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Synthesis, structure and catalytic properties of tripodal amino-acid derivatized pyrazole-based ligands
Abstract
A synthesis of five functional multidendate ligand: methyl 2-(bis((3,5-dimethyl-1H–pyrazol-1-yl)methyl)amino)acetate L1, methyl 2-(bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)amino)-propanoate L2, methyl 2-(bis((3,5-dimethyl-1H-pyrazol-1-yl) methyl) amino)-3-methylbutanoate L3, methyl 2-(bis((3,5-dimethyl-1H-pyrazol-1-yl) methyl) amino)-3-methyl- pentanoate L4 and methyl 6-(bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)amino)hexanoate L5 is reported. Copper (II) complexes of these compounds were examined for their catalytic properties. The in situ generated copper (II) complexes were suitable catalysts for the catalytic oxidation of catechol substrate to quinone with dioxygen at ambient condition. All complexes catalyze the oxidation reaction with the rate varying from a high of 11.8250μmolL−1min−1 for the L2[Cu(CH3CO2)2] complex to a weaker rate of 0.7875μmolL−1min−1 for L3[Cu(NO3)2].
... The development of biomimetic oxidation catalysts, involving the Cu(II) as an active metal center (Gamez et al., 2001;Punniyamurthy et al., 2008), and numerous biomimetic approaches have been devoted to the synthesis of complexes of Cu(II) with various ligands to reproduce the catalytic activity of biological systems containing in their active sites the Cu(II) (El Kodadi et al., 2008;Boussalah et al., 2009;Zerrouki et al., 2011;Bouabdallah et al., 2007a;;Bouabdallah et al., 2007b;Toubi et al., 2012;. ...
... Over the past two decades, many studies, including those in our laboratory, have been devoted to copper complexes carrying nitrogenous heterocyclic ligands (pyrazole, pyridine, imidazole, etc.) to mimic the function of catecholase (Boussalah et al., 2009;Zerrouki et al., 2011;El Kodadi et al., 2008;Bouabdallah et al., 2007a;Bouabdallah et al., 2007b;Mouadili et al., 2013). This research has shown that catecholase activity depends on many factors, including the distance between the two metal centers, the redox potential of the copper centers, the pH, the structure of the ligand, and the nature of the solvent (Boussalah et al., 2009;Zerrouki et al., 2011;El Kodadi et al., 2008;Bouabdallah et al., 2007a;Mouadili et al., 2013;Dey et al., 2016;Paralta et al., 2010;Mendoza-Quijano et al., 2012;Mukherjee et al., 2004;Paul et al., 2017;Mondal et al., 2017;Osorio et al., 2012;Camargo et al., 2015;Neves et al., 2010). ...
... Over the past two decades, many studies, including those in our laboratory, have been devoted to copper complexes carrying nitrogenous heterocyclic ligands (pyrazole, pyridine, imidazole, etc.) to mimic the function of catecholase (Boussalah et al., 2009;Zerrouki et al., 2011;El Kodadi et al., 2008;Bouabdallah et al., 2007a;Bouabdallah et al., 2007b;Mouadili et al., 2013). This research has shown that catecholase activity depends on many factors, including the distance between the two metal centers, the redox potential of the copper centers, the pH, the structure of the ligand, and the nature of the solvent (Boussalah et al., 2009;Zerrouki et al., 2011;El Kodadi et al., 2008;Bouabdallah et al., 2007a;Mouadili et al., 2013;Dey et al., 2016;Paralta et al., 2010;Mendoza-Quijano et al., 2012;Mukherjee et al., 2004;Paul et al., 2017;Mondal et al., 2017;Osorio et al., 2012;Camargo et al., 2015;Neves et al., 2010). ...
In this work, we are interested in finding new catalysts for catecholase, whose principle is based on the oxidation reaction of catechol to o-quinone. We approached the synthesis of the threes tripod ligands based on pyrazole in a condensation reaction and its characterization by IR, 13 C NMR, 1 H NMR spectroscopy, then we evaluated the catalytic properties of certain complexes formed in situ to catalyze the oxidation reaction of catechols to o-quinones. The aim is to find the right models to reproduce the catalytic activity of the enzyme (catecholase), we used complexes formed in situ by pyrazole derivatives with Copper salts. Among these complexes, the complex L4/Cu(CH3COO)2 showed good catalytic activity of the combination (1ligand/2metal) in MeOH for this reaction, with a speed Vmax equal to 69.38 μmol.L-1 .min-1 and a low value of Km equal to 0.019 mol.L-1. We have demonstrated that the nature of concentration, ligand, solvent, and copper salts, influenced strongly the catecholase activity.
... Organotin compounds also play an important role in the field of cross-coupling processes, where they help to build complex organic molecules. These procedures have helped create cutting-edge technology by finding use in the synthesis of sophisticated materials as well as the pharmaceutical industry [18][19][20][21][22][23][24][25][26]. ...
... Furthermore, the application of organotin catalysts in fine chemical synthesis has gained traction, facilitating the productive and sustainable synthesis of specialized chemicals and high-value [19][20][21][22][23][24][25][26][27]. Their capacity to facilitate various chemical transformations under controlled conditions has played a pivotal role in the progression of environmentally friendly chemistry methodologies [28]. ...
... In the literature, we noted studies concerning the synthesis of biomimetic oxidation catalysts to reproduce catecholase activity [24][25][26][27][28][29][30]. Most of the results described use catalysts with the aim of mimicking the metallic active site environment of the catecholase enzyme and also understanding the catalytic properties for activating molecular oxygen. ...
Seven carboxylate Sn(IV) complexes C1–C7 were synthesized by condensation between piperic acid with tri-phenylstannanol C1, piperic acidwith di-butylstannanone C2, phenylthioacetic acid with di-butylstannanone C3, 1,1′-(propane-1,3-diyl)-bis-(5-methyl-1H-pyrazole-3-carboxylic acid) with tri-phenylstannanol C4, 1,1′-(ox-ybis(ethane-2,1- di-yl))bis(5-methyl-1H-pyrazole-3-carboxylic acid) with tri-phenylstannanol C5, 1,1′-(propane-1,3-diyl)-bis-(5-methyl-1H -pyrazole-3-carboxylic acid) with di-butylstannanone C6 and 1,1′-(2-hydroxypropane-1,3-di-yl)bis(5-methyl-1H-pyrazole-3-carboxylic acid) with di-butylstannanone C7 these complexes characterized (by 13C NMR, 1H NMR and IR). Then the elaborated catalytic properties of these complexes were evaluated to catalyze the oxidation reaction of 3,5-di-tert-butylcatechol to 3,5-di-tert-butyl-o-benzoquinone. All the complexes showed good catalytic activity towards the oxidation reaction. Notably, complex C3 emerges as a standout performer, displaying remarkable catalytic activity in the oxidation of 3,5-di-tert-butylcatechol to 3,5-di-tert-butyl-o-benzoquinone. With a reaction rate of 14.45 μmol L−1 min−1 and an astonishing turnover (T) value of 21671.05 cycles per minute, C3 signifies a promising catalyst for future applications.
... The development of biomimetic oxidation catalysts, involving the Cu(II) as an active metal center (Gamez et al., 2001;Punniyamurthy et al., 2008), and numerous biomimetic approaches have been devoted to the synthesis of complexes of Cu(II) with various ligands to reproduce the catalytic activity of biological systems containing in their active sites the Cu(II) (El Kodadi et al., 2008;Boussalah et al., 2009;Zerrouki et al., 2011;Bouabdallah et al., 2007a;;Bouabdallah et al., 2007b;Toubi et al., 2012;. ...
... Over the past two decades, many studies, including those in our laboratory, have been devoted to copper complexes carrying nitrogenous heterocyclic ligands (pyrazole, pyridine, imidazole, etc.) to mimic the function of catecholase (Boussalah et al., 2009;Zerrouki et al., 2011;El Kodadi et al., 2008;Bouabdallah et al., 2007a;Bouabdallah et al., 2007b;Mouadili et al., 2013). This research has shown that catecholase activity depends on many factors, including the distance between the two metal centers, the redox potential of the copper centers, the pH, the structure of the ligand, and the nature of the solvent (Boussalah et al., 2009;Zerrouki et al., 2011;El Kodadi et al., 2008;Bouabdallah et al., 2007a;Mouadili et al., 2013;Dey et al., 2016;Paralta et al., 2010;Mendoza-Quijano et al., 2012;Mukherjee et al., 2004;Paul et al., 2017;Mondal et al., 2017;Osorio et al., 2012;Camargo et al., 2015;Neves et al., 2010). ...
... Over the past two decades, many studies, including those in our laboratory, have been devoted to copper complexes carrying nitrogenous heterocyclic ligands (pyrazole, pyridine, imidazole, etc.) to mimic the function of catecholase (Boussalah et al., 2009;Zerrouki et al., 2011;El Kodadi et al., 2008;Bouabdallah et al., 2007a;Bouabdallah et al., 2007b;Mouadili et al., 2013). This research has shown that catecholase activity depends on many factors, including the distance between the two metal centers, the redox potential of the copper centers, the pH, the structure of the ligand, and the nature of the solvent (Boussalah et al., 2009;Zerrouki et al., 2011;El Kodadi et al., 2008;Bouabdallah et al., 2007a;Mouadili et al., 2013;Dey et al., 2016;Paralta et al., 2010;Mendoza-Quijano et al., 2012;Mukherjee et al., 2004;Paul et al., 2017;Mondal et al., 2017;Osorio et al., 2012;Camargo et al., 2015;Neves et al., 2010). ...
In this work, we are interested in finding new catalysts for catecholase, whose principle is based on the oxidation reaction of catechol to o-quinone. We approached the synthesis of the threes tripod ligands based on pyrazole in a condensation reaction and its characterization by IR, 13C NMR, 1H NMR spectroscopy, then we evaluated the catalytic properties of certain complexes formed in situ to catalyze the oxidation reaction of catechols to o-quinones. The aim is to find the right models to reproduce the catalytic activity of the enzyme (catecholase), we used complexes formed in situ by pyrazole derivatives with Copper salts. Among these complexes, the complex L4/Cu(CH3COO)2 showed good catalytic activity of the combination (1ligand/2metal) in MeOH for this reaction, with a speed Vmax equal to 69.38 μmol.L-1.min-1 and a low value of Km equal to 0.019 mol.L-1. We have demonstrated that the nature of concentration, ligand, solvent, and copper salts, influenced strongly the catecholase activity.
... A wide variety of interesting architectures of complexes based on N,O-donor alcohols results from many variants of their donating capabilities for example: (i) in neutral form: N-monodentate (N) [1], N,O-chelating ( 2 N,O) [2]; and (ii) as deprotonated chelating ( 2 N,O) [2] and bridging (N:O [3], 2 [6]. As a consequence of their special features, N-heteroaromatic alcohols are widely used (i) as a core building material of polynuclear metal complexes (SMMs) [4], (ii) in the preparation of coordination compounds with a broad spectrum of biological activities comprising anticancer [7], antimicrobial [8] and antioxidant [9,10] functions, (iii) as a new catalyst with multipodal ligands based on 1-hydroxymethyl-3,5-dimethylpyrazole [11][12][13][14][15][16], and (iv) as coordination compounds for modelling the structure or function of biomolecules [17,18]. ...
... It is extremely important that the catalytic reaction for compounds modelling Mn-CAT function (14,16,40) occurs under neutral aqueous conditions because the most of synthetic Mn-CAT mimics are insoluble in water and display high activity only in organic solvents [127][128][129]. The catalytic activity of the complexes in the presence of H 2 O 2 in aqueous solution was evaluated, and the evolution of O 2 was monitored using a quadrupole massspectrometer (QMS). ...
... These ligands are analogues of poly(pyrazolyl)borates, called scorpionates which were introduced by Trofimenko [139] and developed by C. and R. Pettrinari [137], Mani et al. [138], and Mukherjee [139], among others. Metal complexes containing such polydentate ligands are particularly interesting because they possess significant applications such as: (i) models for bioinorganic systems (metaloenzymes: CoCA, "blue-copper proteins", bioactive molecules) [17,18], (ii) molecular wires [140], (iii) selective catalysts or their precursors [11][12][13][14][15][16], and (iv) target-specific radiopharmaceuticals [141,142]. ...
... They proposed the first mechanism for bimetallic hydroformylation with a cooperative effect of both metal [13][14]. Otherwise, pyrazole presents a huge importance in coordination chemistry and catalysis as nitrogen rich ligand [15][16][17][18][19][20][21][22][23][24][25]. Herein, we report the synthesis of new pyrazolate Rh and its catalytic activity via the hydroformylation of styrene. ...
... The structure of Head-to-tail PzRh (1) (1):The structure was confirmed by using proton, carbon NMR and X-ray ( Figure 1) (14) -1647 (7) 2928 (5) 7747 (5) 70 (2) Rh (1) 1526 (1) 2620 (1) 10020 (1) 31 (1) Rh (2) -593 (1) 2992 (1) 9157 (1) 33(1) N (6) 415 (4) 1644 (3) 10313 ( (3) 12026 (3) 45(1) C (5) 889 (5) 695 (4) 11538 (4) 36 (1) O (1) 1623 (4) 1086 (3) 11637 (3) 54(1) C (7) 256 (5) 3462 (4) 12089 (4) 39(1) C (4) 174 (5) 963 (4) 10940 (4) 33 (1) C(9) -1731 (5) 3973 (3) 11670 (3) 32 (1) C (2) -1252 (5) 1213 (4) 10306 (4) 35 (1) N(8) -82 (4) 3386 (3) 10691 (3) 29(1) C (20) 447 (5) 2485 (4) 7954 (4) 41 (2) C(27) 3497 (6) 2558 (4) 8297 (4) 53 (2) C (8) -519 (5) 3630 (3) 11504 (3) 30 (1) C (3) -866 (5) 673 (4) 10930 (4) 40 (2) C(28) 2903 (5) 1935 (4) 9026 (4) 40 (2) C (17) -161 (6) 4211 (4) 8429 (4) 45(2) C (21) 3198 (5) 1705 (4) 9781 (4) 45(2) C (19) 1008 (6) 3190 (4) 7284 (4) 52(2) C (24) 2620 (5) 3476 (4) 10190 (4) 47(2) C (25) 2500 (5) 3697 (4) 9369 (4) 41(2) C (18) 907 (6) 4046 (4) 7648 (4) 55(2) C (22) 4175 (6) 2074 (5) 9968 (5) 67(2) C (16) -1337 (6) 4145 (4) 8489 (4) 48 (2) C(13) -755 (6) 2359 (4) 8144 (4) 46 (2) C(26) 3495 (6) 3449 (4) 8559 (4) 52(2) C (6) 1200 (6) -364 (4) 12674 (4) 57(2) C (23) 3731 (6) 2929 (5) 10391 (5) 67(2) C (15) -1700 (7) 3912 (5) 7752 (5) 74 (2) C (1) -2397 (5) 1236 (5) 10049 (4) 57 (2) Rh (3) 6285 (1) 1988 (1) 5009 (1) 30 (1) Rh (4) 4032 (1) 2450 (1) 4320 (1) 31 (1) O (6) 4660 (3) 357 (2) 7875 (2) 41(1) O (7) 1854 (3) 5250 (2) 5620 (3) 40 (1) ...
... C(44)-C(45)- C(46) 126.4(6) C(44)-C(45)-Rh (4) 71.4(4) C(46)-C(45)-Rh (4) 112.1 (4) (14) 80 (6) 101 (6) 44 (5) -7(4) -42(4) -11(5) Rh (1) 29 (1) 30 (1) 36(1) -6(1) -12(1) -5(1) Rh (2) 38 (1) 34 (1) 28 ( (7) 33 (3) 34 (3) 31 (3) -7(2) -13(2) 0(2) C (10) 32 (3) 27 (3) 32 (3) 0(3) -11(3) -4(2) C (11) 37 (3) 33 (3) 35 (4) 1(3) -10(3) -4(3) O (2) 47 (3) 48 (2) 46 (3) 15 (2) -28(2) -13(2) C (5) 38 (4) 34 (3) 33 (4) 1(3) -9(3) -3 (3) O (1) 57 (3) 59 (3) 63 (3) 13 (2) -39(2) -24(2) C (7) 46 (4) 42 (3) 36 ( (8) 30 (3) 30 (2) 31 (3) -7(2) -15(2) 2(2) C (20) 50 (4) 45 (4) 35 ( (8) 34 (3) 29 (3) 29 (3) -4(2) -9(3) -5(2) C (3) 40 (4) 42 (3) 38 (4) 3 (3) -11(3) -17(3) C (28) 28 (3) 40 (3) 48 (4) -13(3) -6(3) 1(3) C (17) 59 (4) 42 (4) 31 (4) 5 (3) -18(3) -2(3) C (21) 29 (3) 44 (4) 57 (5) -8(3) -6(3) -4(3) C (19) 55 (4) 64 (4) 34 (4) -10(3) -10(3) -4(3) C (24) 38 (4) 49 (4) 56 (5) -12(3) -2(3) -26(3) C (25) 44 (4) 37 (3) 45 (4) 3 (3) -15(3) -16(3) C (18) 59 (4) 47 (4) 47 (4) 3 (3) -10(3) 2(3) C (22) 50 (4) 83 (5) 80 (6) -6(5) -38(4) -5(4) C (16) 52 (4) 47 (4) 33 (4) 4 (3) -8 (3) 7(3) C (13) 58 (4) 62 (4) 24 ( (6) 55 (4) 66 (4) 52 (4) 22 (4) -31(4) -12(4) C (23) 59 (5) 92 (6) 63 (5) -12 (4) -27 (4) -26(4) C (15) 61 (5) 93 (6) 66 (5) -8 (5) -35 (4) 21 (4) C (1) 40 (4) 86 (5) 57 (5) 1(4) -23 (3) -28(4) Rh (3) 24 (1) 28 (1) 36 (1) -2(1) -9(1) -1(1) Rh (4) 34 (1) 31 (1) 31 (1) -3(1) -15(1) -6(1) O (6) 42 (2) 47 (2) 34 (2) 8 (2) -17(2) -6(2) O (7) 30 (2) 37 (2) 55 (3) -10(2) -19 (2) 7(2) C(42) 64 (5) 83 (5) 71 (5) -6(4) -42(4) -18(4) O (8) 41 (3) 59 (3) 66 (3) -24 (2) -34(2) 4(2) N (1) 31 (3) 32 (2) 32 (3) -2(2) -10(2) -6(2) N (3) 28 (3) 30 (2) 35 (3) -2(2) -19(2) -1(2) O (5) 36 (2) 64 (3) 42 (3) 6(2) -20(2) -9(2) _______________________________________________________________________ ...
... And a number of non-copper complexes are also found to show a similar kind of activity [34,35]. In this sense, N-heterocyclic derivatives have provided a very useful chelating class selected in the unit assembly leading to the coordination framework for various transition metals such as pyrazole, pyridine and imidazole [36][37][38][39][40][41]. ...
... In general, comparing the activity of our complexes with those reported in previous similar studies shows that the best rate is smaller than that reported for analogous complexes with pyrazole and pyridine based ligands [59], and much lower than some others reported for complexes with tripodal pyrazolyl ring [37,39,40]. Important to note that pyridine and 1,2,4-triazole are more basic than pyrazole, therefore the combination of both triazolyl and pyridyl ring in one tridentate ligand expected that caused an increase in a nity of ligand towards the metal ion, compared to that ligands containing pyrazolyl ring. ...
The discovery of new efficiency therapeutic agents that can block the adhesion of the transmembrane glycoprotein Spike (S-protein) to the human angiotensin-converting enzyme 2 (hACE2) receptor remains one of the most investigated strategies to fight against Covid-19 pandemic. In this context, new triazole derivatives have been synthesized through condensation reactions between (1H-1, 2, 4-triazol-1-yl)methanol and different secondary amines. Their chemical scaffolds were well illuminated by ¹ H/ ¹³ C/ COSY/ HSQC NMR, FT-IR and mass spectroscopies. In silico investigations have been carried out. ADME-Tox screening revealed that the prepared compounds could serve as excellent oral candidate drugs with optimal pharmacokinetic proprieties and toxicological profiles. Molecular docking simulations against the isolated S-RBD protein and SARS-CoV-2-RBD- hACE2 complex showed that our compounds could form important hydrogen, hydrophobic and electrostatic interactions with some key residues that ensure the binding of the S-protein to its hACE2 receptor making them good candidate agents that can block or prevent the entry of SARS-CoV-2 virus in the host cell. Additionally, catecholase activity of the tridentate ligands have been studied. The obtained findings demonstrated that a systematic variation of the ligand substituent and metallic salts types, significantly influences the interaction of the in situ complexes with catechol and hence the oxidase biomimetic catalytic activities. Complex L3/Cu(CH 3 COO) 2 was found to exhibit the highest activity towards oxidation of catechol to its corresponding quinone with a rate of 2.44 𝜇mol.l ⁻¹ .min ⁻¹ .
... The pyrazole derivatives ( Figure 9) investigated in this work were prepared following the experimental procedure of the N-alkylation reaction described previously in the literature [43,46,[60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77]. First, all the compounds were prepared by condensation of primary amines with (3,5-dimethyl-1H-pyrazole-1-yl)methanol or (1H-pyrazole-1-yl)methanol in acetonitrile as a polar aprotic solvent that promotes SN2 reaction; after that, the compounds were purified either by diethyl ether or a DCM:water (3:1) mixture to obtain the final products, with yields varying from 15.22 to 99.41%. ...
... The pyrazole derivatives ( Figure 9) investigated in this work were prepared fol ing the experimental procedure of the N-alkylation reaction described previously in literature [43,46,[60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77]. First, all the compounds were prepared by condensation of mary amines with (3,5-dimethyl-1H-pyrazole-1-yl)methanol or (1H-pyrazole-1-yl)me nol in acetonitrile as a polar aprotic solvent that promotes SN2 reaction; after that compounds were purified either by diethyl ether or a DCM:water (3:1) mixture to ob the final products, with yields varying from 15.22 to 99.41%. ...
A new family of pyrazole-based compounds (1–15) was synthesized and characterized
using different physicochemical analyses, such as FTIR, UV-Visible, 1H, 13C NMR, and ESI/LC�MS. The compounds were evaluated for their in vitro antifungal and antibacterial activities against
several fungal and bacterial strains. The results indicate that some compounds showed excellent
antibacterial activity against E. coli, S. aureus, C. freundii, and L. monocytogenes strains. In contrast,
none of the compounds had antifungal activity. Molecular electrostatic potential (MEP) map analyses
and inductive and mesomeric effect studies were performed to study the relationship between the
chemical structure of our compounds and the biological activity. In addition, molecular docking and
virtual screening studies were carried out to rationalize the antibacterial findings to characterize the
modes of binding of the most active compounds to the active pockets of NDM1 proteins
... In the literature, we noted studies concerning the synthesis of biomimetic oxidation catalysts to reproduce catecholase activity [24][25][26][27][28][29][30]. Most of the results described use catalysts with the aim of mimicking the metallic active site environment of the catecholase enzyme and also understanding the catalytic properties for activating molecular oxygen. ...
It is at the chemistry-biology interface that this work that we have carried out takes place. Indeed, the expected goal is to develop simple molecules, capable of activating the catalytic action of certain metalloenzymes such as tyrosinase. The official name of an enzyme includes the type of reaction catalyzed, the name of the substrates involved. In this work, we carried out the study of the catalytic activity of the complexes of organotin carboxylates synthesized vis-à-vis the oxidation of 3,5-di-tert-butylcatecchol. The results obtained show that the various complexes exhibit good catalytic activity for the oxidation of 3,5-di-tert-butylcatecchol under mild conditions. The complexes that showed good catalytic activity are the compounds C1 and C2.
... In recent years, several biomimetic approaches have been devoted, to reproduce catecholase and phenoxazinone synthase activity and to better understand its properties to activate dioxygen (O 2 ). Synthetic chemical compounds, based on pyrazole, represented the best model, for mimicking the active site of metalloproteins [22][23][24][25][26][27], considering that pyrazole has a similar structure as imidazole, and it is easier to introduce into the synthesis of flexible structures. On the other hand, pyrazole-based ligands are widely used in the synthesis of transition metal coordination compounds [28], and they can act as terminal or proximate ligands [29,30]. ...
In situ complexes, arising from six ligands based on pyrazol (L1-L6): N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-4-fluoroaniline (L1); 5-chloro-N-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)pyridin-2-amine (L2); N-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-N-phenylaniline (L3); N-((1H-pyrazol-1-yl) methyl)-N-phenylbenzenamine (L4); N,N-bis((1H-pyrazol-1-yl)methyl)-4-fluoroaniline (L5); and N-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)aniline (L6), were reported and examined, in combination with different metallic salts, for their catecholase and phenoxazinone synthase activities at ambient conditions. We highlight the utility of spectroscopic and electrochemical methods, for studying the catalytic activity of biomimetic complexes and understanding the catalytic mechanism of substrate oxidation; the electrochemical oxidation of catechol has been successfully performed by cyclic voltammetry at room temperature and electrochemical cell with three electrodes. The role of metallic salt and the ligand structure of these complexes on their catecholase and phenoxazinone synthase activity have been examined. The metallic salt Cu(CH3COO)2 appears a better candidate to produce the best model of the two studied enzymes in neutral mediums.
... d Optimized geometry of the Cu 2+ complex with L1 Table 7 Torsion angles of the optimized geometry of the isolated complex L1-Cu(II) in (b) conformation (Fig. 9b In the literature, several complexes with pyrazole moiety have been used in the study of catechol oxidation, and described as having the potential activity to oxidize catechols. Concerning the catalytic activity of the complexes studied towards the oxidation of catechol, some researchers have reported oxidation rates of catechol equal to 1.46 μmol l −1 min −1 , 4.38 μmol l −1 min −1 , and 11.83 μmol l −1 min −1 for the best catalyst [28,29,40]. ...
Syntheses of two new multidentate poly((3,5-dimethylpyrazol-1-yl)methyl)benzene ligands have been carried out by alkylation process of pyrazoles with poly(bromomethyl) using the t-BuOK/THF. The ¹H-NMR, ¹³C-NMR, and IR spectroscopic data of these ligands have been fully assigned. The crystalline structure of one compound was completely determined by single-crystal X-ray diffraction at 111 K and room temperature together with the isobaric thermal expansion. The catecholase activity studies were investigated using absorption measurements in methanol. The in situ complexes of the multidentate ligands have been found able to oxidize the catechol substrate. The results demonstrated that factors like molar ratio of oxidant-to-substrate, nature of ligand, metal ion, and counter-ion significantly influence the catalytic activities. Complex L1/Cu(CH3COO)2, in the 1:2 molar ratio, exhibits the highest activity towards oxidation of catechol to its corresponding quinone with a rate of 4.46 μmol l⁻¹ min⁻¹. DFT calculations were performed in order to predict the most probable geometry of the organometallic complexes formed by these two new ligands and copper (II) ions.
... The functional pyrazolyl derivatives 94-100 were prepared by condensing two equivalents of (3,5-dimethyl-1H-pyrazole-1-yl)methanol with one equivalent of amino acid ester hydrochloride derivatives (commercially available) in anhydrous solvents. All reactions were carried out at room temperature under stirring conditions for 4 to 6 days in an inert atmosphere [42,[97][98][99][100][101][102][103][104][105][106]. ...
Bayoud disease affects date palms in North Africa and the Middle East, and many researchers have used various methods to fight it. One of those methods is the chemical use of synthetic compounds, which raises questions centred around the compounds and common features used to prepare targeted molecules. In this review, 100 compounds of tested small molecules, collected from 2002 to 2022 in Web of Sciences, were divided into ten different classes against the main cause of Bayoud disease pathogen Fusarium oxysporum f. sp. albedinis (F.o.a.) with structure–activity relationship (SAR) interpretations for pharmacophore site predictions as (δ−···δ−), where 12 compounds are the most efficient (one compound from each group). The compounds, i.e., (Z)-1-(1.5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy but-2-en-1-one 7, (Z)-3-(phenyl)-1-(1,5-dimethyl-1H-pyrazole-3-yl)-3-hydroxyprop-2-en-1-one 23, (Z)-1-(1,5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy-3-(pyridine-2-yl)prop-2-en-1-one 29, and 2,3-bis-[(2-hydroxy-2-phenyl)ethenyl]-6-nitro-quinoxaline 61, have antifungal pharmacophore sites (δ−···δ−) in common in N1---O4, whereas other compounds have only one δ− pharmacophore site pushed by the donor effect of the substituents on the phenyl rings. This specificity interferes in the biological activity against F.o.a. Further understanding of mechanistic drug–target interactions on this subject is currently underway.
... These experiences aim to mimic the environment of the metal active site of this enzyme and also to better understand this function which is often assigned to metalloproteines containing copper like catechole oxidase [14], which is known to have two copper (II) ions similar to histidine nitrogen's ligands [15], this enzyme catalyses the oxidation of catechol to corresponding o-quinone through the four-electron reduction of molecular oxygen to water [16]. In attempt to mimic the active site function of catechol oxidase, many ligands models based on iron [17], copper [18], and cobalt [19] complexes have been designed and extensively studied [20][21][22][23][24][25][26][27][28][29][30][31][32]. In the continuation of looking for other ligands to be tested in such reaction comes this work which concerns azo compounds [33][34][35]. ...
In order to mimic the function of catecholase activity, in situ copper (II) complexes of five ligands containing benzene and naphthalene moieties ponded by dazenyl groups: (E)-1-((2-methoxyphenyl)diazenyl)naphthalen-2-ol L1, (E)-1-((3-methoxyphenyl)diazenyl)naphthalen-2-ol L2, (E)-1- ((4-methoxyphenyl)diazenyl)naphthalen-2-ol L3, (E)-1-((2,4,6-tribromophenyl)diazenyl)naphthalen-2-ol L4, and (E)-1-((3-nitrophenyl)diazenyl)naphthalen-2-ol L5 were reported and examined, in combination with different copper salts, for their catecholase activities at ambient conditions. All complexes of tested ligands catalyze the studied reaction with the rate ranging from higher 25.1 µmol L⁻¹ min⁻¹ for the combination of two equivalents of ligand and one equivalent of metal in methanol, to weaker rate of 0.51 µmol L⁻¹ min⁻¹ for the combination of one equivalent of ligand and two equivalent of metal salt in methanol.
... Copper complexes, as well as other elements of the first transition series, such as iron and zinc, participate in many biochemical processes and can be used as catalysts in many oxidation reactions [3]. The development of biomimetic oxidation catalysts, involving the Cu (II) ion as the active metal center, has received great attention in recent decades [4,5], and many biomimetic approaches have been devoted to the synthesis of complexes of Cu (II) ion with various ligands to reproduce the catalytic activity of biological systems containing in their active sites the Cu (II) ion [6][7][8][9]. The aim of the studies is to understand the properties of an enzyme to activate molecular oxygen. ...
Catalysis is a branch of chemical kinetics that, more generally, studies the influence of all physical or chemical factors determining reaction rates. It solves a lot of problems in the chemistry reaction process, especially for a green, economic and less polluting chemistry. For this reason, the search for new catalysts for known organic reactions, occupies a very advanced place in the themes proposed by the chemists. The present review reports the recent progress (2000-2019) on catechol oxidase activity.
... In addition, N-(hydroxyalkyl) pyrazole is often explored as a proligand to obtain ligands of the N-scorpionate [2][3][4][5][6][7][8][9] or pincer type [10]. The metal complexes containing such polydentate ligands are particularly interesting because they have important applications such as: models for bioinorganic systems (metaloenzymes: CoCA,''blue-copper proteins", bioactive molecules) [11,12], molecularwires [13], selective catalysts or their precursors [14][15][16][17][18][19], and target-specific radiopharma-ceuticals [20,21]. Barium and Mercury complexes have been extensively studied in this area [22][23][24][25] For this reason, we decided to investigate the ability of the hydroxypyrazole (Hdpz) to form complexes of Barium and Mercury. ...
The reaction of the didenate N, O donor ligand 1-hydroxymethyl-3,5-dimethylpyrazole (Hdpz) with Ba(NO3)2 and HgSO4 in a molar ratio 1: 1 (M: L) leads to interesting complexes [BaNO3(Hdpz)].2H2O and HgSO4(Hdpz) with good yields. Hdpz, [BaNO3(Hdpz)].2H2O and HgSO4(Hdpz) were synthesized and characterized using different physicochemical methods such as FTIR, ¹H NMR, ¹³C NMR and MS. The DFT theoretical studies have been carried out to calculate certain parameters of reactivity such as the molecular electrostatic potential analysis (MESP) and the calculation of maxima and minima points of MESP.
... As shown in Fig. 1, L1 geometry is wide which can creates more steric hindrance around the metal center. As result, the complex geometry is affected and the activity is rise [46]. In each case, the activities of cobalt complexes are more important than that of copper one (Fig. 8) [12]. ...
... The progress of the catechol oxidation reaction is conveniently followed monitoring the strong absorbance peak of o-quinone in the UV/Vis spectrophotometer (Scheme 2). The metal complex (prepared in situ from metal salt and the ligand) [47] and a solution of catechol were added together in the spectrophotometric cell at 25 C [48,49]. Formation of o-quinone was monitored by the increase in absorbance at 390 and 400 nm as a function of time. ...
Three new Schiff bases compounds (L1-L2-L3) were synthesized by a condensation reaction in 1:1 M ratios of dehydroacetic acid (3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione) and 4-fluoro/4-chloro/4-bromo aniline in ethanol, the products were obtained in excellent yields. Their structures were characterized by spectroscopic techniques (FT-IR and 1H NMR) and single-crystal X-ray diffraction. The three compounds display zwitterionic forms, with cationic iminium and anionic enolate groups. The aromatic ring and dehydroacetic acid ring are in a trans position with respect to the C[dbnd]N bond. Calculations in the framework of the density-functional theory (DFT) were carried out to determine the optimized structures and electronic properties as the HOMO-LUMO energy gap. Hirshfeld surface analysis was used to support the packed crystal lattice 3D network intermolecular forces. The NH form is found to be more stable than OH form. On the other hand, the in situ generated copper (II) complexes were examined for their catalytic activities and were found to catalyze the oxidation reaction of catechol to o-quinone under atmospheric dioxygen. The present study reveals that the rate of oxidation depends on the nature of the substituents in the phenyl ring, the counter anion and the concentration of ligand. The combination L1(Cu(CH3COO)2) gives the highest rate.
... It is clear that the hydrazone-pyrazole derivatives, in particular ligand L6, described in this work present further improvement and show better values and higher activity for the effective aerobic oxidation of the catechol into o-quinone. [29] bipyrazolic tripode-prop-2-ylacetate Cu(CH 3 COO) 2 11.825 [30] bipyrazolic tripode-4-hydroxyphenyl CuCl 2 1.458 [31] bipyrazolic tripode-3-hydroxypropyl CuSO 4 28.990 [32] bipyrazolic tripode-3-hydroxypropyl CuCl 2 4.378 [33] indole-3-chalcone Cu(CH 3 COO) 2 31.780 [34] [(3,5-dimethyl-pyrazol-1-ylmethyl)-amino]-propionitrile CuSO 4 8.710 [35] The superior catalytic activity observed for ligand L6 is probably due to the stability of corresponding copper complex (catalyst) favored by the organic conjugate π bonds of the three benzene ring contained in the ligand and by the intense coordination bonds of the Schiff base. ...
The development of low-cost catalytic systems that mimic the activity of tyrosinase enzymes (Catechol oxidase) is of great promise for future biochemistry technologic demands. Herein, we report the synthesis of new biomolecules systems based on hydrazone derivatives containing a pyrazole moiety (L1–L6) with superior catecholase activity. Crystal structures of L1 and L2 biomolecules were determined by X-ray single crystal diffraction (XRD). Optimized geometrical parameters were calculated by density functional theory (DFT) at B3LYP/6–31G (d, p) level and were found to be in good agreement with single crystal XRD data. Copper (II) complexes of the compounds (L1–L6), generated in-situ, were investigated for their catalytic activities towards the oxidation reaction of catechol to ortho-quinone with the atmospheric dioxygen, in an attempt to model the activity of the copper containing enzyme tyrosinase. The studies showed that the activities depend on four parameters: the nature of the ligand, the nature of counter anion, the nature of solvent and the concentration of ligand. The Cu(II)-ligands, given here, present the highest catalytic activity (72.920 μmol·L−1·min−1) among the catalysts recently reported in the existing literature.
... The synthetic route of target pyrazoles was illustrated in (Scheme 1). Compounds a and b were already reported by several old and recent works (Boussalah et al. 2009;Dvoretzky and Holmes 1950). All the pyrazolic compounds excepting 15, 16, and 18-20 were already described and published in the literature (Abrigach et al. 2014;Khoutoul et al. 2015;El Kodadi et al. 2004). ...
A series of new pyrazolic heterocyclic compounds were prepared in good and excellent yields and characterized by proton and carbon nuclear magnetic resonance, infrared, and mass spectroscopy studies. These products were screened in vitro against three bacterial pathogens, namely Bacillus subtilis, Micrococcus luteus, and Escherichia coli and antifungal potential, against Fusarium oxysporum f.sp.albedinis. A considerable and excellent activity was recorded with respect to the two studied microorganisms. A good correlation was obtained between the experimental results and the theoretical predictions of bioavailability using Petra/Osiris/Molinspiration suite (Petra/Osiris/Molinspiration containing Lipinski’s rule-of-five). The quantitative structure activity relationship approach has been analyzed to support the Petra/Osiris/Molinspiration results and composite indexes of some quantum chemical parameters were constructed in order to characterize the inhibition performance of the tested molecules.
... The methylene protons are diastereotopic in the chiral ligand 5a (Fig. (1)) and their signals appear as AB systems with a coupling constants of 13 Hz. Very sensitive probes for changes in the environment are the methylene proton resonances which agree with the reported literature [33][34][35]. ...
A new library of N,N,N',N'-tetradentate pyrazoly compounds containing a pyrazole moiety were synthesized by the condensation of (3,5-dimethyl-1H-pyrazol-1-yl)methanol 2a or (1H-pyrazol-1-yl)methanol 2b with a series of primary diamines in refluxed acetonitrile for 6h. The antifungal activity against the budding yeast Saccharomyces cerevisiae, as well as the antibacterial activity against Escherichia coli of these new tridentate ligands were studied. We found that that these tetradentate ligands act specifically as antifungal agents and lack antibacterial activity. Their biological activities depend on the nature of the structure of the compounds.
... Polypyrazolic ligands have diverse applications in pharmacology (Park et al., 2005; Tewari and Mishra, 2001; Finn et al., 2003; Yahyi et al., 2010), biology (Radi et al., 2010; Janus et al., 1999; Pimerova and Voronina, 2001; Michon et al., 1995; Bailey et al., 1985), and catalysis (Sorrell et al., 1984; Boussalah et al., 2009) and electronics (Marzin et al., 1987; Steel and Constable, 1990). They are also used in extraction, complexation and the transport of some alkaline and transition metals (Tarrago et al. 1988; Malek et al., 2002 Malek et al., , 2005a Radi et al., 2006; Malek and Radi, 2009). ...
Three tridentate N,N-bis(3,5-dimethylpyrazol-1-ylmethyl)-1-hydroxy-2-aminoethane (2), N,N-bis(3,5-dimethylpyrazol-1-ylmethyl)-cyclohexylamine (3) and 2-[bis(1,5-dimethyl-1H-pyrazol-3-ylmethyl)amino]ethan-1-ol (4) are synthesized and spectroscopically characterized together with 1-hydroxymethyl-3,5-dimethylpyrazole (1). These have been tested in inhibitory activities against various hyperactive enzymes like urease, β-glucuronidase, phosphodiesterase, α-chymotrypsin, acetylcholinesterase and butyrylcholinesterase. Compounds 1, 2 and 3 were found to be selective inhibitors of urease. Compound 4 was found to be selective inhibitor of butyrylcholinesterase. The nature of the junction between pyrazoles cycles determined the activities of these tripods. While the tripods are inactive towards urease or glucuronidase, they turn to be selective towards butyrylcholinesterase.
... In addition, we are very interested in the study of their catalytic activities such as isomerization [19,20] and oxidation reactions. [21][22][23] To our knowledge, the 1,2,4-triazole unit has never been incorporated into a tridentate symmetrical structure (-N-CH 2 -N-junction) or screened for biological activities. We report here an easy and facile synthesis of seven new N,N-bis(1,2,4-triazolyl)amines containing new bulky aromatic groups at the central nitrogen atom with diverse substituants. ...
New N,N-bis(triazol-1-ylmethyl)amines have been prepared in one step by condensation of 1-(hydroxymethyl)triazole with a series of primary substituted aromatic amines. These reactions were carried out in refluxed CH3CN for 4 h. The products were recuperated with excellent and good yields (75–90.5%). The x-ray crystallography structure of one of them has been studied.
A novel double-open-cubane (NNCO)6Co4Cl2 cluster with a Co4O6 core was made available under aqua-ultrasonic open atmosphere conditions for the first time. The ultrasonic clusterization of the (3,5-dimethyl-1H-pyrazol-1-yl)methanol (NNCOH) ligand with CoCl2·6H2O salts in ethanol yielded a high-purity and high-yield cluster product. Energy-dispersive X-ray (EDX), Fourier transform infrared (FT-IR), and ultraviolet (UV)-visible techniques were used to elucidate the clusterization process. The double-open-Co4O6 cubane structure of the (NNCO)6Co4Cl2 cluster was solved by synchrotron single-crystal X-ray diffraction (SXRD) and supported by density functional theory (DFT) optimization and thermogravimetric/differential TG (TG/DTG) measurements; moreover, the DFT structural parameters correlated with the ones determined by SXRD. Molecular electrostatic potential (MEP), Mulliken atomic charge/natural population analysis (MAC/NPA), highest occupied molecular orbital/lowest unoccupied molecular orbital (HOMO/LUMO), density of states (DOS), and GRD quantum analyses were computed at the DFT/B3LYP/6-311G(d,p) theory level. The thermal behavior of the cluster was characterized to support the formation of the Co4O6 core as a stable final product. The catalytic property of the (NNCO)6Co4Cl2 cluster was predestined for the oxidation process of 3,5-DTBC diol (3,5-di-tert-butylbenzene-1,2-diol) to 3,5-DTBQ dione (3,5-di-tert-butylcyclohexa-3,5-diene-1,2-dione).
The high catalytic activity of catechol oxidation in atmospheric oxygen signified the selectivity and efficiency of the metalloenzyme [CuSO4L], with L is 5 chloro-N-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)pyridin-2-amine. In this study, two parameters influencing the catecholase activity were examined: the nature of solvent and the nature of the complex. The best activity of catechol oxidation is given by the synthesized complex in methanol solvent with the rate of 1.7 μmol/L min⁻¹. In the contrary, the prepared complex in situ (weak catalyst) showed weak value in the oxidation rate (0.14 μmol/L min⁻¹) in DMSO.
However, our complex synthesized in good yield was subjected to several spectral and thermal analyses to verify the results obtained.
Symmetrical azine ligand-based (L1-L6) have been evaluated for their catecholase activity by combining them in situ with different metal salts, the complexes exhibited significant catalytic activity in oxidizing catechol to o-quinone at ambient conditions in the presence of dioxygen as an oxidant, especially for the combination of L4/CuCl2 with molar ratio [1L/1M] with Vmax of 50,24 μmol L⁻¹ min⁻¹ and with Km equal to 0,0215 mol L⁻¹, the study showed that several parameters are contributed on the catalytic activity of mimicking enzymes such as the nature of Ligand, ion metal, counter anion, the concentration of ligand and substrate. Kinetic parameters have been determined for the best combinations following the Michaelis Menten and the results obtained are in agreement with this model.
Five-membered ring systems containing two nitrogen atoms adjacent to each other are called pyrazoles. This article serves to cover the comprehensive literature on pyrazoles during the 10 year period 2008–18. The previous two articles of this volume series on pyrazoles dealt more with the theoretical, experimental structural and thermodynamic methods and less with the reactivity, synthetic and applications of pyrazoles. The last article and the last 10 years, more literature have appeared on the synthesis and reactivity of the pyrazole ring systems. Also, the pyrazole core has been utilized as a reagent in modern synthetic reactions and as agricultural/pharmaceutical drugs. This article will focus on these current developments.
The purpose of this study is to demonstrate the synthesis of pyrazole-based ligands and to evaluate their catalytic properties in the oxidation reaction of catechol to o-quinone. The ligands were prepared via the condensation of (3,5-dimethyl-1H pyrazol-1-yl)methanol A with the appropriate primary amine. Four pyrazole-based ligands were successfully synthesized and characterized. These ligands provide one pyrazole sp2-nitrogen, one pyridine sp2-nitrogen, and one amine sp3-nitrogen, which were capable of coordinating to the metal. For evaluating the catalytic activity, the experiments were tested by varying the type of solvent, metal ion, anion in the metal salt, and ratios of ligands and metal salts. Excellent catalytic activities for the oxidation of catechol to o-quinone were obtained. The copper (II)-based complexes showed better reactions rates than those based on other metals (e.g., nickel, tin, and barium), which was due to the fact that the active catalytic site of the catecholase enzyme has two active sites from the existence of copper (II) ions. The composition ratios of ligands and metal salts as well as the type of anion in the metal salt bring impacts to the formation of complexes. We found also that the type of solvent contributes to the interaction and dilution of reactants in the solvent. This study demonstrated that the present ligands can be used as a model for further developments in catalytic processes relating to catecholase activity.
A novel [Ni4(µ3-O)4] twisted cubane complex, Ni4Cl2(NN)2(ONN)2(NNO)2(H2O)2·2THF, was prepared from a crude mixture of three bidentate ligands. A mixture of ethyl 1-(hydroxymethyl)-3-methyl-1H-pyrazole-5-carboxylate (HONN) and ethyl 1-(hydroxyl-methyl)-5-methyl-1H-pyrazole-3-carboxylate (NNOH) were added to ethyl 3-methyl-1H-pyrazole-5-carboxylate (NNH) then mixed to NiCl2·6H2O solution under ambient conditions. Reaction progress was monitored via infrared and ultraviolet–visible spectroscopies and energy-dispersive X-ray spectroscopy was used to analyze the product. Reaction yields for cluster synthesis were very good. Single crystal structure determination for the cluster indicates a novel [Ni4(µ3-O)4] twisted cubane structure with octahedral geometry around each of the Ni(II) centers in Ni4Cl2(NN)2(ONN)2(NNO)2(H2O)2·2THF. The lattice is stabilized by hydrogen bonding and H–\( \pi \) stacking. Hirshfeld surface analysis (HSA) corroborates the single crystal structure determination results. The cluster displays significant thermal stability under open atmosphere conditions; it decomposes in three steps at high temperature. The cluster demonstrates promising results as a catalyst; it promoted the complete oxidation of catechol to o-Quinone in under mild conditions.
The reaction of hydroxymethyl pyrazole derivatives with one equivalent of the appropriate primary amine yields N-((1h-pyrazol-1-yl) methyl) pyrimidin-2-amine (L1), 2-(((1h-pyrazol-1-yl) methyl) amino) benzoic acid (L2), and ethyl 5-methyl-1-(((6-methyl-3-nitropyridin-2-yl) amino) methyl)-1h-pyrazole-3-carboxylate (L3). The structure of synthesized compounds (L1-L3) was identified by FT-IR, UV–visible, proton NMR spectroscopy, mass spectroscopy, and single crystal X-ray crystallography. The armed pyrazoles (L1-L3) were crystallized in the space groups C2/c, P21/n and P-1 for L1, L2, and L3 respectively. Crystallographic analysis revealed that N–H of the amine group and Nitrogen or Oxygen atoms are in-plane with the aromatic ring. The aminomethyl chain forms a distorted second plane. The angle between the two planes is observed to be 76.07° (N2–C7–N5–N19) for L1, 62.12° (N34–C63–N22–N35) for L2, 60.84° (N3–C8–N2–N1), and 0.41° (N1–C4–C3–O1/O2) for L3 was studied. Theoretical physical and chemical properties calculations have been performed on the studied armed pyrazoles (L1-L3) using three different programs: Petra, Osiris, & Molinspiration (POM). The geometric parameters of the optimized structure are in agreement with the experimental data obtained from the X-ray structures. The origin of the biological activity against breast cancer and microbes has also been confirmed.
The napthyl/pyridine-pyrazole-derived complexes, [Mn(L¹)Cl2] (1), [Co(L¹)Cl2] (2), [Cu(µ-Cl)(Cl)(L)]2 (3), [Cu2(L)2(N3)3(µ2-N3)] (4), and [Co(L²)Cl2] (5) (where L¹ = bis-(3,5-dimethyl-pyrazol-1-ylmethyl)-napthalen-1-ylmethyl-amine (L¹), L = 5-methyl-pyrazol-1-ylmethyl) -napthalen-1-ylmethyl-amine (L) and L² = 2-[2-(3,5-dimethyl-pyrazol-1-yl)-1-methyl-ethyl]-pyridine), exhibited phenoxazinone synthase activity in methanol in the range 5–54 h⁻¹. Binuclear copper(II) derivatives 3 and 4 show better catalytic activities than manganese(II) and cobalt(II) derivatives. The kinetic studies reveal that phenoxazinone chromophore is produced via a complex-substrate intermediate. Further, 3 and 4 show catecholase activity in methanol in the presence of oxygen. All the complexes showed potent antimicrobial activity against the tested strains of bacteria and fungi. Complex 1 was synthesized for the first time by mixing L¹ and MnCl2 (1:1) and characterized by single-crystal X-ray crystallography, cyclic voltammetry, density functional theory, and thermogravimetry analysis. The present study suggests that napthyl/pyridyl-anchored pyrazole metal complexes are interesting scaffolds for the development of novel model compounds for biochemical reaction and efficient antimicrobial agents.
In situ syntheses and X-ray structures of three novel cationic–anionic complexes: [CoL1Br][ZnL2L3ZnBr5] (1), and [CoL1Cl][ZnL3Br3] (2) and [CoL1Cl][ZnL3Cl3] (3) L1 = N,N,N-tris(3,5-dimethylpyrazol-1-ylmethyl)amine, L2 = hexamethylenetetramine (urotropine), L3 = 3,5-dimethylpyrazole, have been reported. The presence of three different organic ligands (L1, L2 and L3) in isolated complexes results from various reactions taking place in the system which contains zerovalent cobalt and 1-hydroxymethyl-3,5-dimethylpyrazole as starting materials, in the presence of Zn(II) ions. The scorpionate-type ligand (L1) formed in situ, possesses four potential donor sites, specifically three nitrogen donor atoms from the pyrazole rings, and one from tertiary amine, all of which coordinate to Co(II). They form a distorted trigonal bipyramidal [CoL1X]+ cation whereas anionic parts include tetrahedrally coordinated zinc(II). The crystal structures and electronic (UV-Vis), infrared (FT-IR) spectra and thermal investigation of the isolated complexes have been analysed and discussed. Finally, the biological activity of 1–3 complexes was assessed. All the tested complexes expressed higher selectivity towards human cancer cells than towards human normal cells and showed a substantial antitumor activity against: colorectal adenocarcinomas Caco-2 and SW 620, hepatocellular carcinoma Hep G2 and lung carcinoma A549.
The in-situ transition metal complexes of five ligands L1-L5 were reported and examined for their catecholase activities at ambient conditions, we found that reaction rate depends on five parameters: Nature of the ligand; nature of metal salts, concentration of the combination of metal/ligand; nature of solvent and nature of the substrate. The highest rate activity is given by the in-situ complex formed by ligand L1 and metal salt Cu(CH3CO2)2 which is equal to 19.04 μmol.L-1min-1.
Six bidentate pyrazole ligands L1-L6 have been prepared, Bis(1H-pyrazol-1yl)methane L1, 3,5-Dimethyl-1- pyrazol-1-ylmethyl-1H-pyrazole L2, (bis(3,5-dimethyl-1H-pyrazol-1-yl)methane L3, Ethyl 1-((3,5-dimethyl- 1H-pyrazol-1-yl)methyl)-5-methyl-1H-pyrazole-3-carboxylate L4, Ethyl 1-((1H-pyrazol-1-yl)methyl)-5- methyl-1H-pyrazole-3-carboxylate L5, Ethyl-1-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-5-phenyl-1Hpyrazole- 3-carboxylate L6. Copper (II) complexes of these compounds were examined for their catalytic properties. The in situ-generated copper (II) complexes were suitable catalysts for the catalytic oxidation of catechol substrate to quinone with dioxygen at ambient condition. All complexes catalyze the oxidation reaction with the rate varying from a high of 25.0854μmolL-1min-1 for the L6/[Cu(CH3CO2)2] complex in THF to a weaker rate of 0.0645μmolL-1min-1 for L1/[CuCl2]. The preliminary results show that the oxidation rate depends on different parameters such as the concentration, solvent and the metal anions.
The reaction of dehydroacetic acid DHA carboxaldehyde and RCHO derivatives (R = quinoleine-8-; indole-3-; pyrrol-2- and 4-(dimethylamino)phenyl - afforded four new chalcone ligands (4-hydroxy-6-methyl-3-[(2E)-3-quinolin-8-ylprop-2-enoyl]-2H-pyran-2-one) L1, (4-hydroxy-3-[(2E)-3-(1H-indol-3-yl)prop-2-enoyl]-6-methyl-2H-pyran-2-one) L2, (4-hydroxy-6-methyl-3-[(2E)-3-(1H-pyrrol-2-yl)prop-2-enoyl]-2H-pyran-2-one) L3, and (3-{(2E)-3-[4-(dimethylamino)phenyl]prop-2-enoyl}-4-hydroxy-6-methyl-2H-pyran-2-one) L4. L3 and L4 were characterized by X-ray crystallography. Molecules crystallize with four and two molecules in the asymmetric unit, respectively and adopt an E conformation about the C=C bond. Both structures are stabilized by an extended network O-H ... O. Furthermore, N-H ... O and C-H ... O hydrogen bonds are observed in L3 and L4 structures, respectively. The in situ generated copper (II) complexes of the four compounds L1, L2, L3 and L4 were examined for their catalytic activities and were found to catalyze the oxidation reaction of catechol to o-quinone under atmospheric dioxygen. The rates of this oxidation depend on three parameters: ligand, ion salts and solvent nature and the combination L2[Cu (CH3COO)2] leads to the faster catalytic process.
A comparative study of new activity catecholase using complex based on three compounds type pentylidene-(4-vinyl-phenyl)-amine L1, butylidene-(4-vinyl-phenyl)-amine L2, sopentylidene-(4-methoxy-phenyl)-amine L3 has been reported. This study was performed to examine the catalytic effect of the in situ-generated copper (II) complexes towards catechol oxidation reaction with atmospheric dioxygen at room temperature. All complexes catalyze the studied reaction with the rate varying from a higher 9.5625 μmol L-1 min-1 for the L2[Cu(CH 3 CO 2) 2 ] to a weaker of 0.2500 μmol L-1 min-1 for L2[Cu(NO 3) 2 ]. The duplicating of ligand concentration influences in different way the oxidation rates. Against with an excess of catechol, the oxidation rate becomes very low.
In order to mimic the function of catecholase activity, in-situ copper (II) complexes of three ligands containing different numbers of benzyl groups: (E)-4-methoxy-N-(4-methoxybenzylidene)aniline L 1 , (E)-N-(4-methoxybenzylidene) naphthalene-1-amine L 2 , (E)-N-(4-methoxybenzylidene)aniline L 3 , were reported and examined, in combination with different cupric salts, for their catecholase activities at ambient conditions. The highest rate activity was given by the combination of two equivalents of L 3 and one equivalent of Cu(CH 3 COO) 2 in methanol. The Michaelis-Menten model was applied to obtain the kinetic parameters of the best catalyst.
In this study, we investigated the inhibition of the corrosion of carbon steel (CS) in acidic solution by 2-[Bis-(3,5-dimethyl-pyrazol-1-ylmethyl)-amino]-pentanedioic acid (Bip1) was studied against carbon steel corrosion, in acidic environment using weight loss and electrochemical measurements. The inhibition efficiency increased with increasing inhibitor's concentration, but decreased with the increase in temperature. Bip1 acted as a highly efficient mixed type inhibitor. Adsorption of used inhibitor led to a reduction in the double layer capacitance and an increase in the charge transfer resistance. The high inhibition efficiency was attributedto the blocking of active sites by adsorption of inhibitor molecules on the steel surface. The adsorption of Bip1 on the carbon steel surface obeyed Langmuir adsorption isotherm. The inhibition mechanism was further corroborated by the values of activation parameters obtained from the experimental data.
Abstract
The corrosion and inhibitors adsorption processes in mild steel / two tripodal pyrazolic compounds
namly3-[Bis-(3,5-dimethyl-pyrazol-1-ylmethyl)-amino]-propan-1-ol(Tpyr1) and 1-[Bis-(3 carbomethoxy-
5-methyl-pyrazol-1-ylmethyl)-amino]-propan-2-ol (Tpyr2) / hydrochloric acid systems were studied at
different temperatures (308-323 K) by means weight loss (WL) measurements. It has found that the
studied compounds exhibit a very good performance as inhibitors for mild steel corrosion in 1.0 M HCl.
Results show that the inhibition efficiency increases with decreasing temperature and increasing
concentration of inhibitors. It has been determined that the adsorption for the studied inhibitors on mild
steel complies with the Langmuir adsorption. The kinetic and thermodynamic parameters for mild steel
corrosion and inhibitor adsorption were determined and discussed, respectively. On the bases of
thermodynamic adsorption parameters, comprehensive adsorption (physisorption and chemisorption) for
the studied inhibitors on mild steel surface has been suggested.
A series of seven heterocyclic compounds based on pyridazinone and thiopyridazinone moieties: 5-(2-chlorobenzyl)-6-methylpyridazin-3-one L1; 5-[(2-chlorobenzyl)hydroxyl)methyl]6-methylpyridazin-3-one L2; 5-(2-chlorobenzyl)-2,6-dimethylpyridazin-3-one L3; 5-(2-chlorobenzyl)-2-(hydroxyethyl)-6-methylpyridazin-3-one L4; ethyl-4-(2-chloro-benzyl)-3-methyl-6-oxopyridazin-1(6H)-yl)acetate L5; 5-(2-chlorobenzyl)-2-(hydroxyethyl)-6-methylpyridazin-3-thione L6, and ethyl-4-(2-chloro-benzyl)-3-methyl-6-thioxopyridazin-1(6H)-yl)acetate L7 were tested for the oxidation of catechol to o-quinone for miming microorganism in the O2 activation for electrophilic non substituted aromatic. The in situ generated Cu(II), Fe(II) and Zn(II) complexes of these ligands (L1–L7) were examined for such catalytic activities. We found that all these substrates catalyze the oxidation reaction of catechol to o-quinone with the presence of atmospheric dioxygen. The rates of this oxidation depend on two parameters: the nature of the ligand and the nature of ion salts. We found that the combination of L7 [Cu(CH
3
COO)2
] leads to the fastest catalytic processes.
The synthesis of series of tripodal ligands: N,N-bis((3-carboxyethyl-5-dimethyl-1H-pyrazol-1-yl)methyl)phenylamine L1, N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)phenylamine L2, N,N-bis((3-carboxyethyl-5-dimethyl-1H-pyrazol-1-yl)methyl)pyridin-2-ylamine L3, N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)pyridin-2-amine L4, N,N-bis((3-carboxyethyl-5-dimethyl-1H-pyrazol-1-yl)methyl)-2-nitrophenylamine L5, N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-2-nitrophenylamine L6 were reported. Copper (II) complexes of these compounds prepared in-situ were examined for their catalytic oxidative activities. The effect of the nature of the ligand, the substrate and the copper salts on the catecholase activities will be also investigated. Mechanistic studies were also discussed.
A series of heterocyclic compounds possessing imidazolo[1,2-a]pyridine moiety, namely, ethyl 7-methylimidazolo[1,2-a] pyridine-2-carboxylate L1; 2-(3-nitrophenyl)imidazo[1,2-a]pyridine L2; 3-(imidazo[1,2-a]pyridine-2-yl)aniline L3; 2-phenylimidazolo[1,2-a]pyridine-3carbaldehyde L4; and 2-phenylimidazo[1,2-a]pyridine L5 were synthesized. The in situ generated copper (II), iron (II), and zinc (II) complexes of these compounds (L1–L5) were examined for their catalytic activities and were found to be effective catalysts for the oxidation of catechol to o-quinone with the atmospheric oxygen. The present study reveals that the rate of oxidation depends on four parameters: the nature of the ligand, transition metals, ion salts, and the concentration of the complex. The combination L2(Cu(CH
3
COO)
2
) gives the highest rate.
We have studied the oxidation of catechol to o-quinone with atmospheric dioxygen at ambient conditions by in situ generated copper (II) complexes of five electron-rich nitrogen ligands: (3,5-dimethyl-pyrazol-1-yl)-methanol L1; 3-benzylamino-propionitrile L2; 3-[benzyl-(3,5-dimethyl-pyrazol-1-ylmethyl)-amino]-propionitrile L3; {3-[(2-cyano-ethyl)-(1,5-dimethyl-1H-pyrazol-3-ylmethyl)-amino]-propyl}-(1,5-dimethyl-1H-pyrazol-3-ylmethyl)-amino]-propionitrile L4 and 3-[{2-[(2-cyano-ethyl)-(1,5-dimethyl-1H-pyrazol-3-ylmethyl)-amino]-ethyl}-(1,5-dimethyl-1H-pyrazol-3-ylmethyl)-amino]-propionitrile L5. We found that all complexes catalyze the oxidation reaction with different rates depending on three parameters: the nature of the ligand, the nature of ion salts, and the concentration of the complex. The combination of L3(CuSO4) gave the highest rate of this activity about 8.71 μmol1/L1/min1.
The in situ copper (II) complexes of six pyrazole and pyridine based ligands: 1-[5-methyl-1-pyridin-2-yl-1H-pyrazol-3-yl] methanol L1, 2-(3,5-dimethyl-pyrazol-1-yl)-pyridine L2, (5-methyl-3-pyridin-2-yl-1H-pyrazol-1-yl) ethyl acetate L3, 1′,5,5′-trimethyl-1′H-1,3′-bipyrazol-3-ethyl carboxylat L4, (1′,5,5′-trimethyl-1′H-1,3′-bipyrazol-3-yl) methanol L5, and 5,5′-diphenyl-3,3′-bipyrazole L6, are reported and studied for their catecholase activities at ambient conditions, the reaction rate depends on four parameters: The nature of the carbonic chain bounded to the pyrazole ring, the nature of counter anion, the concentration of ligand and the nature of solvent. The highest rate activity is given by complex resulting from one equivalent of ligand L4 and two equivalents of Cu(CH3COO)2 in methanol, which equal to 4.440 μmol L−1 min−1.
A synthesis of three new tripodal ligands: 3-[bis-(3,5-dimethyl-pyrazol-1-ylmethyl)-amino]-propan-1-ol L1, 3-[bis-(5-methyl-3-carbomethoxy-pyrazol-1-ylmethyl)-amino]-propan-1-ol, L2 and 3-[bis-(5-methyl-3-carboethoxy-pyrazol-1-ylmethyl)-amino]-propan-1-ol L3 is reported. The in situ-generated copper(II) complexes of three new compounds (L1–L3) were examined for their catalytic activities and were found to catalyse the oxidation reaction of catechol to o-quinone with the atmospheric dioxygen. These activities depend on the nature of the ligand and the copper salts.
Herein we report the development of efficient methods to prepare monodentate, bidentate, tridentate and macrocycle compounds based on pyrazole moieties, with the opportunity to change easily structure, substituents, cavities or all these parameters in the synthesis of huge library compounds. These methods take advantage of the vast number of commercially available starting materials containing functional and aliphatic or aromatic amines. Such as structural and electronic diversity makes these approaches well suited to the production of large arrays of compounds for potential application in medicinal, corrosion or coordination chemistry.
Oxygen is a highly atom-economical, environmentally benign, and abundant oxidant, which makes it ideal in many ways. The high activation energies in the reactions of oxygen require that catalysts be employed. A number of alternate approaches have been developed allowing oxidation chemistry to be used safely across a broader array of conditions. For example, use of carbon dioxide instead of nitrogen as a diluent leads to reduced flammability. Alternately, water can be added to moderate the flammability allowing even pure oxygen to be employed. New reactor designs also allow pure oxygen to be used instead of diluted oxygen by maintaining gas bubbles in the solvent, which greatly improves reaction rates and prevents the build up of higher concentrations of oxygen in the head space. Oxidation occurs through two primary mechanisms. In acidic or activated substrates, deprotonation can occur, followed by single-electron oxidation to form the key radical species that then reacts with molecular oxygen.
Series of functional multidendate ligands based on pyrazole and amino acid derivatives were prepared in good and excellent yields (75–5%) by condensation of one equivalent of amino acid ester hydrochloride substrates with two equivalents of (3,5-dimethyl-1H–pyrazol-1-yl)metha-nol. These tridentate functionalized compounds and their starting materials were screened for their antifungal activities against Fusarium oxysporum f.sp. albedinis and the yeast of Saccharomyces cerevisiae. Considerable activities were recorded with respect to the two studied microorganisms. ª 2011 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.
RESUME: L'addition d'un équivalent de diéthyl isopropylamine sur une suspension d'un équivalent de la glycine méthyle ester sous sa forme chlorhydrate dans le DMF anhydre. Le mélange réactionnel est agité pendant 5 minutes, alors on rajoute goutte à goutte a ce mélange réactionnel une solution de deux équivalents du hydroxylméthyl-(3,5-diméthyl)pyrazole dans un minimum de DMF anhydre, sous atmosphère inerte. La réaction est agitée pendant quatre jours à température ambiante. Ensuite elle est acidifiée, extraite par l'éther, séchée, filtrée et concentrée on obtient un liquide qui donnera par la suite des cristaux. La structure cristalline a été confirmée par diffraction aux rayons X. Le produit cristallise dans le groupe d'espace P21/n avec une superposition du dimer par des interactions π-π. ABSTRACT: One equivalent of diethylisopropyleamine was added to a suspension of one equivalent of glycine methylester hydrochloride in anhydrous DMF. The mixture was stirred under nitrogen for 5 minutes and a solution of two equivalents of (3,5-dimethyl-1H-pyrazol-1-yl)methanol in anhydrous DMF was added dropwise. The reaction was allowed to stir from four days under nitrogen atmosphere at room temperature. The mixture was dissolved in water and the compound was extracted by diethyl ether. The organic layers was washed with saturated brine solution, dried, filtered and concentrated to yield the oils which gives mono crystal. The structure was confirmed by X-ray crystal with monoclinic P21/c group, having good π-π interactions.
New organotin (IV) based on 2-(thiophene-2-yl)acetic acid and 1-H-pyrazole-3-carboxylic acid derivatives 1-ae and 2a-e was prepared and characterized by IR, 1H and 13C NMR spectroscopy. These reactions were carried out under refluxing conditions using CHCl3 / EtOH (3:1) as solvents and 2:1 / 1:1 acid / metal oxide rations. The tin products were recuperated with moderate and good yields (55-85%). The Compounds (1b, 1e and 2e) were screened for their antitumor activities against two human tumor cell lines: HeLa, an epithelial cell from a fatal cervical carcinoma and HEK293, an embryonic kidney tumor. All three materials show an activity in vitro against these cell lines.
A newly prepared ligand, N,N-bis(pyrazol-1-ylmethyl)benzylamine (L) reacted with metal ions to form [FeLCl3], [NiL(NCS)2(MeOH)], [MLX2](M = CoII, CuII or ZnII, X = Cl–, Br– or NCS–) and [(CuLI)2]. The crystallographically determined structures of [CoLCl2] and [CoL(NCS)2] reveal the co-ordination sphere of cobalt(II) to be intermediate between distorted tetrahedral and trigonal bipyramidal. In [NiL(NCS)2(MeOH)] the co-ordination sphere of nickel(II) ion is distorted octahedral while that of copper(II) in [CuLCl2] is distorted square pyramidal. The complex [(CuLI)2] displays distorted tetrahedral geometry around copper(I), and [ZnLBr2] shows distorted tetrahedral geometry around zinc(II).
The tridentate ligand N,N-Bis(3,5-dimethylpyrazol-1-ylmethyl)-1-hydroxy-2-aminoethane (L) has been prepared in one step by condensation of two equivalents of 1-hydroxymethyl-3,5-dimethylpyrazole with one equivalent of 2-aminoethanol. This reaction is carried out under microwave irradiation (60 W) in the absence of solvent for 20 min [1]. Using this ligand L a new Cu(II) dinitrate complex has been prepared. The singlecrystal X-ray structure of the title compound, [N,N-bis(3,5-dimethylpyrazol-1-ylmethyl)-1-hydroxy-2-aminoethane] (3,5-dimethylpyrazole)copper(II) dinitrate, revels that the copper (II) ion is coordinated to two pyrazole nitrogens, one tertiary amine nitrogen of the ligand L and 3,5-dimethylpyrazole, and in the apical position by an alcohol O atom.
In many crustaceans, changing concentrations of several low molecular weight compounds modulates hemocyanin oxygen binding, resulting in lower or higher oxygen affinities of the pigment. The nonphysiological effector caffeine and the physiological modulator urate, the latter accumulating in the hemolymph of the lobster Homarus vulgaris during hypoxia, increase hemocyanin oxygen affinity and decrease cooperativity of oxygen binding. To derive a model that describes the mechanism of allosteric interaction between hemocyanin and oxygen in the presence of urate or caffeine, studies of oxygen, urate, and caffeine binding to hemocyanin were performed. Exposure of lobster hemocyanin to various pH values between 7.25 and 8.15 resulted in a decrease of p50. In this pH interval, p50 decreases from 95 to 11 Torr without effectors and from 49 to 6 Torr and from 34 to 5 Torr in the presence of 1 mM urate or caffeine, respectively. Thus, the allosteric effects induced by protons and urate or caffeine are coupled. In contrast, isothermal titration calorimetry did not reveal any differences in binding enthalpy (DeltaH degrees ) for urate or caffeine under either normoxic or hypoxic conditions at different pH values. Despite these apparently conflicting results, they can be explained by the nested MWC model if two different types of modulator binding sites are assumed, an allosteric and a nonallosteric type of site. Simulations of in vivo conditions with this model indicate that the naturally occurring modulator urate is physiologically relevant in H. vulgaris only during hypoxic conditions, i.e., either during environmental oxygen limitation or extensive exercise.
Äußerst überraschend war die Erkenntnis, daß Peptidnucleinsäuren (PNAs, B=Nucleobase) trotz ihrer drastisch vom natürlichen DNA-Rückgrat abweichenden Struktur besser als die meisten Oligonucleotidderivate als Nucleinsäuremimetica genutzt werden können. Die Synthese, physikalischen Eigenschaften und biologischen Wechselwirkungen sowohl der PNAs als auch ihrer Chimären mit DNA und RNA werden hier zusammenfassend beschrieben.
Copper is a bioessential element in biology with truly unique chemical characteristics in its two relevant oxidation states +I and +II. Significant progress has been made in recent years in the elucidation of the frequently surprising biochemistry of this trace element. Those advances were especially furthered through mutual stimulation involving results from biochemistry, molecular biology, and medicine on one hand and the synthesis as well as the structural and spectroscopic characterization of low molecular weight model complexes on the other. The most notable features of protein-bound active copper are its almost exclusive function in the metabolism of O2 or N/O compounds (NO, N2O) and its frequent association with oxidizing organic and inorganic radicals such as tyrosyl, semiquinones, superoxide, or nitrosyl. This unique biological role of copper can be rationalized given its chemical and assumed evolutionary background.
Three new octadentate ligands, namely (R)-N,N′-dimethyl-N,N′-bis{3-[bis(1-methyl-2-imidazolylmethyl)]aminopropyl}-1,1′-binaphthyl-2,2′-diamine, (R)-DABN-3Im4, (R)-N,N′-dimethyl-N,N′-bis{4-[bis(1-methyl-2-benzimidazolylmethyl)]aminobutyl}-1,1′-binaphthyl-2,2′-diamine, (R)-DABN-4Bz4, and (S)-N2,N6-dimethyl-N2,N6-bis{2′-[bis(1-methyl-2-benzimidazolylmethyl)]aminomethyl}benzyl-2,6-diamino-1-exanol acetate, l-Lys-4Bz4, were employed for the synthesis of dinuclear and trinuclear copper(II) complexes. The ligands contain two side arms of different nature and length which carry tridentate aminobis(benzimidazole) or aminobis(imidazole) residues as metal binding sites (A sites) connected to a central (R)-1,1′-binaphthyl-2,2′-diamine or l-lysine residue which can bind a third metal ion (B site). The chiroptical properties of the ligands and the complexes have been described. The complexes were tested as catalysts in the oxidation of 3,5-di-tert-butylcatechol, l-, d-Dopa and l-, d-Dopa methyl esters by dioxygen to give the corresponding quinones. The catalytic efficiency is moderate, but the complexes exhibit significant enantio-differentiating ability towards l-, d-Dopa methyl esters, albeit their enantio-differentiating ability towards l-, d-Dopa is lower. The (R)-1,1′-binaphthyl-2,2′-diamine spacer in the (R)-DABN complexes has much stronger recognition power than the aliphatic l-lysine spacer in the l-Lys complexes. In addition, the highest stereoselectivity in the catalytic oxidation is obtained with the (R)-DABN-3Im4 complexes, containing carbon chains of three atoms between the (R)-1,1′-binaphthyl-2,2′-diamine groups and the tridentate donor units at the A metal binding sites. In all cases, the preferred enantiomeric substrate has the l configuration, which is dictated by the chirality of the spacer residue.
Two macroacyclic ligands represented as L1 and L2 with 3N2O and 5N donor atoms, respectively, have been synthesized by Schiff base condensation. They were subsequently grafted on a silica surface via covalent bonds. The organic ligands L1 and L2 as well as the heterogenized ligands L1·SiO2 and L2·SiO2 reacted with copper(II) leading to the formation of dinuclear copper(II) complexes. Catalytic oxidation of 3,5-di-t-butylcatechol (DTBC) by dioxygen was studied using as catalysts the homogeneous Cu2(L1) and Cu2(L2) and the heterogenized Cu2(L1)·SiO2 and Cu2(L2)·SiO2 complexes. These complexes were found to be very effective catalysts for DTBC oxidation producing mainly 3,5-di-t-butylquinone (DTBQ). During the catalytic process the formation of an o-semiquinone radical has also been confirmed. The immobilized on modified silica surface copper(II) complexes gave significantly higher DTBC conversion than the homogeneous copper(II) complexes.
Copper(II) salts were combined with a tetrapyrazolyl ligand ({N,N,N’,N’-tetrakis-[(3,5-dimethylpyrazol-1-yl)methyl)-1,4-phenylenediamine}L1 or {N,N,N’,N’-tetrakis-[(1,5-dimethylpyrazol-3-yl)methyl)-1,4-phenylenediamine}L2) and assessed as oxidation catalysts. The corresponding dioxygen complexes were generated in situ by mixing the copper salt and the pyrazolyl donor ligand in air. The oxidation of 3,5-di-tert-butylcatechol (DTBC), which affords 3,5-di-tert-butylquinone (DTBQ), was studied. The reaction rate was found to depend essentially on the nature of the junction linking two pyrazolyl neighbours.
Äußerst überraschend war die Erkenntnis, daß Peptidnucleinsäuren (PNAs, B=Nucleobase) trotz ihrer drastisch vom natürlichen DNA-Rückgrat abweichenden Struktur besser als die meisten Oligonucleotidderivate als Nucleinsäuremimetica genutzt werden können. Die Synthese, physikalischen Eigenschaften und biologischen Wechselwirkungen sowohl der PNAs als auch ihrer Chimären mit DNA und RNA werden hier zusammenfassend beschrieben.
Wie DNA-Photolyasen sind Modellproteine, die die Flavin-Aminosaure L-1 innerhalb der DNA-Bindungsregion eines Transkriptionsfaktors enthalten, in der Lage, in einzelstrangigen Oligonucleotiden Pyrimidindimer-Schaden vollstandig zu reparieren. Die Cyclobutan-Pyrimidindimere werden dabei photochemisch reaktiviert.
Reaction of ZnCl2 with a new ligand N,N-bis(3,5-dimethylpyrazolylmethyl)-l-alaninemethylester (bdmpame) in methanol gives [ZnCl2(bdmpame)]. The structure of [ZnCl2(bdmpame)]·CH2Cl2 has been resolved by X-ray crystallographic analysis. The Zn atom has a distorted tetrahedral geometry involving a nitrogen atom from each pyrazole in bdmpame and two chloro ligands with bond lengths in the range 2.037(4)–2.237(2) Å. The nitrogen atom of the l-alaninemethylester group in the compound was not coordinated to the metal center, giving an eight-membered ring in which the nitrogen atoms of each pyrazole in bdmpame are coordinated to the metal center. The results of the catalytic enantioselective reduction of acetophenone promoted by ligand/Zn(OTf)2=1:1 mole ratio in the presence of catecholborane for 48 h at 0°C gives (S)-(−)-1-phenylethanol in 21% ee with 68% yield.
Palladium complexes immobilized onto generations 0–3 PAMAM dendrimers supported on silica, in the presence of 1,4-bis(diphenylphosphino)butane, were used as catalysts for the cyclocarbonylation of 2-allylphenols, 2-allylaniline, 2-vinylphenol and 2-vinylaniline affording five-, six- or seven membered ring lactones and lactams. Good conversions were realized using the catalytic system, and the catalyst was recycled 3–5 times. The influence of the spacer chain was investigated, as well as the solvent and the CO/H2 ratio, on the selectivity and the recyclability of the cyclocarbonylation reactions.
Evidences are provided that catechols [as copper(II)catecholates] are the actual primary products of copper-mediated (catalysed) ortho-selective oxidation of phenols, on the contrary to a recent claim reporting direct generation of ortho-quinones.
A series of three new quadridentate ligands was synthesized by reaction of the haloacetylated amino acid esters L-BrAc−Phe−OMe (4a), L-BrAc−Lys(Z)−OMe (4b), and ClAc−Gly−OEt (4c), respectively, with bis(picolyl)amine (bpa, 5). The obtained products L-bpaAc−Phe−OMe (3a), L-bpaAc−Lys(Z)−OMe (3b), and bpaAc−Gly−OEt (3c) were treated with Zn(OTf)2 (OTf = CF3SO3−) to yield the trigonal-bipyramidal complexes [(L-bpaAc−Phe−OMe)ZnOTf](OTf) (6a), [(L-bpaAc−Lys(Z)−OMe)ZnOTf](OTf) (6b), and [(bpaAc−Gly−OEt)ZnOTf](OTf) (6c). Crystal structures of 6c and the hydrolysis product [(L-bpaAc−Phe−OMe)(H2O)ZnOTf](OTf)2 (7a) are reported. The results suggest the formation of a chiral pocket at the metal center provided by the benzyl substituent in the L-phenylalanine derivative 7a. This observation is further supported by 1H-NMR and circular dichroism spectroscopic data. These methods indicate a significant ordering effect within the ligands upon metal coordination as well as interactions between the first coordination spheres and their chiral environments provided by the L-phenylalanine and L-lysine moieties of 3a and 3b, respectively. Our results are discussed with respect to the development of chiral building blocks for transition metal catalysts and biomimetic assemblies.
Discusses studies done in modeling the copper centers in the proteins hemocyanin (a dioxygen carrier), tyrosinase, and dopamine beta-hydroxylase. Copper proteins, model approach in copper bioinorganic chemistry, characterization of reversible oxygen carriers and dioxygen-metal complexes, a copper mono-oxygenase model reaction, and other topics are considered. (JN)
Five new N,N-bis(pyrazole-1-yl-methyl) alkylamines have been prepared in one step by condensation of two equivalents of 1-(hydroxymethyl)-3,5-disubstituted pyrazoles with a series of primary amines. This reaction is carried out under microwave irradiation (60 W) in the absence of solvent for 20 m and affords high yields (75–90%) of mixed nitrogen donor tripodal molecules.
A synthesis of new tripodal ligand: N,N-bis[(1,5-dimethylpyrazol-3-yl)methyl]benzylamine is reported. Copper (II) complexes of compounds: N,N-bis(3,5-dimethylpyrazol-1-ylmethyl)-amines (L1–L5) and N,N-bis[(1,5-dimethylpyrazol-3-yl)methyl]-amines (L6–L9) were examined for their catalytic activities. The dioxygen complexes of copper (II) were generated in situ by stirring copper salts and the tridentate pyrazole ligands. It has been found that the oxidation of 3,5-di-tert-butylcatechol is very efficient to give 3,5-di-tert-butylquinone. Ligand structure has proven critical in controlling not only the formation of complexes but also their subsequent reactivity. The nature of junction between the pyrazolic rings and the benzene have a large effect on the oxidation reaction rate.
A new tripodal ligand, N,N-bis(3,5-dimethylpyrazol -1-ylmethyl)-1-hydroxy-2-aminoethane (bpmhe), has been synthesized. Using this ligand, Cu(II) complexes of the type [Cu(bpmhe)X]Y where X = H2O, NO3, Br, Cl, or N3 and Y = BF4, NO3, Br, or Cl have been prepared. This has resulted in the formation of mononuclear five-coordinate complexes as shown by UV-Vis spectroscopy and Fast Atom Bombardment Mass Spectrometry. The complexes were tested for their reactivity towards the oxidation of catechol to quinone by following the appearance of quinone spectrophotometrically. The complexes show differing rates of reaction depending on the nature of the exogenous fifth ligand with the azido complex showing the fastest rate of oxidation.
Efficiencies of the incorporation of various nonnatural amino acids carrying aromatic side groups into streptavidin were examined. The aromatic amino acids were linked to a mixed dinucleotide, pdCpA, and the resulting aminoacyl pdCpAs were coupled with tRNAcccg(−CA) to afford chemically aminoacylated tRNAcccg's. Mutant streptavidin mRNA containing a CGGG 4 base codon at the Tyr83 site was prepared and added to an Escherichia coli in vitro translation system with the aminoacyl tRNAcccg. The expression of the full-length mutant streptavidins was confirmed by a Western blot analysis, and their biotin binding activity was examined by a dot blot analysis. The Western blot analysis indicated that the efficiencies of the incorporation were higher for aromatic groups with straight configurations than those with widely expanded or bend configurations. The incorporation efficiencies were also examined in a rabbit reticulocyte lysate. In the latter system, the efficiencies were markedly improved for nonnatural amino acids with large side groups such as pyrene and anthraquinone.
Oligopeptide amphiphiles with different dipeptide moieties of −XYNH2 (X = Gly and Ala, Y = Gly, Ala, Val, Leu, and Phe) were synthesized. Binding of aqueous dipeptides onto monolayers of equimolar mixtures of these amphiphiles with a benzoic acid amphiphile (2C18BCOOH) was investigated by π−A isotherm measurement, FT-IR spectroscopy, and XPS elemental analysis. For given GlyX dipeptides (X = neutral and hydrophobic residues), the binding ratio was lessened with increasing sizes of the side chain of the Y residue in the GlyY dipeptide moiety of the host amphiphiles. The Langmuir-type saturation behavior was observed for binding of GlyLeu to an equimolar monolayer of 2C18BGly2NH2 and 2C18BCOOH. Its binding constant of 475 M-1 was 10 times larger than that observed for a single-component monolayer of 2C18BGly2NH2 (K = 35 M-1). The saturation guest/host ratio was 0.47. The mode of substrate insertion into the binding site was examined by FT-IR spectroscopy. When the hydrophobic residue was on the C-terminal of a guest dipeptide (GlyX), the C-terminal insertion was selected with accompanying formation of cyclic carboxylic acid dimers at the interface. In the case of XGly guests, the N-terminal insertion with salt bridge formation with the host was observed. When the two residues of a dipeptide had close hydrophobicities, both C- and N-terminal insertions were observed. Formation of these binding sites is apparently induced by dipeptide binding.
Sugar amino acids (SAAs) were designed and synthesized as new non-peptide peptidomimetics utilizing carbohydrates as peptide building blocks. They represent sugar-like ring structures that carry an amino and a carboxylic functional group and have a specific conformational influence on the backbone of peptides due to their distinct substitution patterns in rigid pyranose sugar rings. Five different SAAs (SAA1α, SAA1β, SAA2, SAA3, and SAA4) have been synthesized that show the ability to constrain linear backbone conformations or distinct turn structures. Linear and cyclic peptides involving SAAs have been prepared in solution as well as by solid phase synthesis. SAA1α and SAA2 were incorporated into two linear Leu-enkephalin analogs, replacing the natural Gly-Gly dipeptide. NMR studies provide evidence for the conformation-inducing effect of the carbohydrate moiety. SAA2 and SAA3 have been placed in cyclic hexapeptide analogs of somatostatin; SAA4 was incorporated in a model peptide. The conformation of the cyclic peptides cyclo(-SAA2-Phe-d-Trp-Lys-Thr-), cyclo(-SAA3-Phe-d-Trp-Lys(Boc)Thr(tBu)-), and cyclo(-SAA4-Ala-d-Pro-Ala-Ala-) have been analyzed by various NMR techniques in combination with distance geometry calculations and subsequent molecular dynamic simulations. The determined solution conformations were compared to representative idealized peptide backbones. SAA2 and SAA3 induce a β-turn structure while SAA4 mimics a γ-turn. Both enkephalin analogs were not active in the guinea pig ileum assay. The somatostatin analog containing SAA2 has an inhibition constant (IC50) of 0.15 μM for the inhibition of the release of growth hormone.
A new tripodal ligand, 5-(bis(3,5-dimethyl-1H-pyrazol-1-ylmethyl)amino)pentan-1-ol, has been synthesized. Three functional, N-donor tripodal pyrazolyl ligands, L1: 2-(bis(3,5-dimethyl-1H-pyrazol-1-ylmethyl)amino)ethan-1-ol; L2: 4-(bis(3,5-dimethyl-1H-pyrazol-1-ylmethyl)amino)butan-1-ol and L3: 5-(bis(3,5-dimethyl-1H-pyrazol-1-ylmethyl)amino)-pentan-1-ol have been examined for their catalytic oxidative activities. The dioxygen complexes of copper (II) were generated in situ by stirring copper salts and the tridentate pyrazole ligands. It has been found that these compounds are very efficient to give quinone. The lengths of the lateral chain carrying the hydroxyl group and the nature of the anion copper (II) salts have been investigated. These two parameters play an important effect on the oxidation reaction rate.
A series of dinuclear CuII complexes of reduced Schiff bases from substituted salicylaldehydes and amino acids have been synthesized and characterized. They are: [Cu2(RScp11)2(H2O)2] {H2RScp11 = 1-[(2-hydroxy-5-R-benzyl)amino]cyclopentane-1-carboxylic acid; R = H (1), Cl (2), CH3 (3), OH (4)}, [Cu2(RSch11)2(H2O)x] {H2RSch11 = 1-[(2-hydroxy-5-R-benzyl)amino]cyclohexane-1-carboxylic acid; R = H and x = 1 (5), R = Cl and x = 2 (6), R = CH3 and x = 2 (7)}, [Cu2(RSch12)2(H2O)2] {H2RSch12 = 2-[(2-hydroxy-5-R-benzyl)amino]cyclohexane-1-carboxylic acid; R = H (8), CH3 (10) and [Cu2(ClSch12)2]·2H2O (9)}, [Cu2(Diala5)2(H2O)2]·H2O [H3Diala5 = N-(2,5-dihydroxybenzyl)-L-alanine] (11), [Cu2(Diala4)2(H2O)2]·H2O [H3Diala4 = N-(2,4-dihydroxybenzyl)-L-alanine] (12), and [Cu2(Diala3)2(H2O)2]·H2O [H3Diala3 = N-(2,3-dihydroxybenzyl)-L-alanine] (13). They were isolated and characterized by chemical and spectroscopic methods. Single crystal X-ray crystallographic studies have revealed that [Cu2(Scp11)2(MeOH)2] (1a), [Cu2(ClScp11)2(DMF)(H2O)]·MeCN (2a), [Cu2(MeScp11)2(MeOH)2]·2 MeOH (3a), [Cu2(ClSch11)2(MeOH)2]·2 MeOH (6a), [Cu2(ClSch12)2]·2 MeOH (9a), and [Cu2(Diala4)2(DMSO)2]·2 DMSO·2 acetone (12a) have 1D hydrogen-bonded polymeric structures while 4 has a 3D hydrogen-bonded network structure. Complex 8 displays a 2D coordination polymeric network structure. The complexes 1–13 have been investigated as functional models for the catechol oxidase by employing 3,5-di-tert-butylcatechol as a model substrate. Electron-withdrawing substituents reduced the activity while electron-donating substituents enhanced the activity. Variable-temperature magnetic studies conducted on compound 8 suggest the presence of strong inter-dimer antiferromagnetic coupling. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
An unnatural peptide-based library, bound on a solid support, was screened for double-stranded-DNA (dsDNA)-binding ligands. For this purpose, fluorescein and rhodamine were used to label the single-stranded oigodeoxynucleotides. Beads containing products with affinity to dsDNA turned red in visible light and fluoresced yellow in UV light. A similar technique can be used for the selection of ligands which bind to a hairpin RNA, using a monolabelled oligoribonucleotide. The screening process revealed a high structure-affinity relationship in the successful products. Only six out of the twelve unnatural amino acids were selected, with the repeated appearance of AlaU, Sar and the secondary amino acids (Hyp, Inp). The affinity and selectivity for the target was determined using a DNase I protection assay.
Recently determined structures of copper-containing plant catechol oxidase in three different catalytic states have provided new insights into the mechanism of this enzyme and its relationship to other copper type-3 proteins. Moreover, the active site of catechol oxidase has been found to be structurally conserved with the oxygen-binding site of a molluscan hemocyanin.
Dipeptide crystals containing nanochannels of various sizes show remarkable and selective absorption of methane, carbon dioxide and hydrogen.
Hemocyanins are giant oxygen transport proteins found in many arthropods and molluscs. Freely dissolved in the hemolymph, they are multisubunit proteins that contain many copies of the active site, a copper atom pair that reversibly binds oxygen. Octopus hemocyanin is composed of ten subunits, each of which contain seven oxygen-binding "functional units". The carboxyl-terminal 47 kDa functional unit, Odg, is a proteolytic isolate that binds oxygen reversibly while exhibiting slight Bohr and magnesium ion effects. In this work we present the X-ray structure determination and analysis of Odg at 2.3 A resolution. Odg has two structural domains: a largely alpha-helical copper binding domain, and a five-stranded anti-parallel beta-sandwich with the jelly roll topology found in many viruses. Six histidine residues ligate the copper atoms, one of which is involved in a thioether bridge. The results show that the hemocyanin from the mollusc and that from the arthropod have distinct tertiary folds in addition to the long recognized differences in their quaternary structures. Nonetheless, a comparison of Octopus and horseshoe crab hemocyanin reveals a similar active site, in a striking example of perhaps both convergent and divergent evolution.
Catechol oxidases are ubiquitous plant enzymes containing a dinuclear copper center. In the wound-response mechanism of the plant they catalyze the oxidation of a broad range of ortho-diphenols to the corresponding o-quinones coupled with the reduction of oxygen to water. The crystal structures of the enzyme from sweet potato in the resting dicupric Cu(II)-Cu(II) state, the reduced dicuprous Cu(I)-Cu(I) form, and in complex with the inhibitor phenylthiourea were analyzed. The catalytic copper center is accommodated in a central four-helix-bundle located in a hydrophobic pocket close to the surface. Both metal binding sites are composed of three histidine ligands. His 109, ligated to the CuA site, is covalently linked to Cys 92 by an unusual thioether bond. Based on biochemical, spectroscopic and the presented structural data, a catalytical mechanism is proposed in which one of the oxygen atoms of the diphenolic substrate binds to CuB of the oxygenated enzyme.
Bioinspired copper-model-complexes that react with O(2) provide an opportunity to probe biological reactivity at a small-molecule level of detail. Biological structural information combined with appropriate ligand design has proven sufficient to create Cu:O(2) complexes capable of external substrate oxidation. Most notable developments during the review period are the bioinspired catalysts capable of aerobic alcohol-oxidation. The extension of this oxidative reactivity to other important organic transformations beyond the scope of the inspiring system completes a modeling paradigm.
The enzymes tyrosinase, catecholoxidase and hemocyanin all share similar active sites, although their physiological functions differ. Hemocyanins serve as oxygen carrier proteins, and tyrosinases and catecholoxidases (commonly referred to as phenoloxidases in arthropods) catalyze the hydroxylation of monophenols or the oxidation of o-diphenols to o-quinones, or both. Tyrosinases are activated in vivo by limited proteolytic cleavage, which might open up substrate access to the catalytic site. It has recently been demonstrated that if hemocyanins are subjected to similar proteolytic treatments (in vitro) they also exhibit at least catecholoxidase reactivity. On the basis of their molecular structures, hemocyanins are used as model systems to understand the substrate-active-site interaction between catecholoxidases and tyrosinases.
The peptide-zinc complex [(Dpg-Phe)Zn]2+
(Dpg =
N,N-dipicolylglycine; Phe = phenylalanine) reversibly forms a homochiral P-helical coordination polymer upon switching the pH from mildly basic to mildly acidic.
Attempting to model superoxide dismutase (SOD) enzymes, we designed two new N3O-donor ligands to provide the same set of donor atoms observed in the active site of these enzymes: K(i)Pr2TCMA (potassium 1,4-diisopropyl-1,4,7-triazacyclononane-N-acetate) and KBPZG (potassium N,N-bis(3,5-dimethylpyrazolylmethyl) glycinate). Five new Co(II) complexes (1-5) were obtained and characterized by X-ray crystallography, mass spectrometry, electrochemistry, magnetochemistry, UV-vis, and electron paramagnetic resonance (EPR) spectroscopies. The crystal structures of 1 and 3-5 revealed five-coordinate complexes, whereas complex 2 is six-coordinate. The EPR data of complexes 3 and 4 agree with those of the Co(II)-substituted SOD, which strongly support the proposition that the active site of the enzyme structurally resembles these models. The redox behavior of complexes 1-5 clearly demonstrates the stabilization of the Co(II) state in the ligand field provided by these ligands. The irreversibility displayed by all of the complexes is probably related to an electron-transfer process followed by a rearrangement of the geometry around the metal center for complexes 1 and 3-5 that probably changes from a trigonal bipyramidal (high spin, d7) to octahedral (low spin, d6) as Co(II) is oxidized to Co(III), which is also expected to be accompanied by a spin-state conversion. As the redox potentials to convert the Co(II) to Co(III) are high, it can be inferred that the redox potential of the Co(II)-substituted SOD may be outside the range required to convert the superoxide radical (O2*-) to hydrogen peroxide, and this is sufficient to explain the inactivity of the enzyme. Finally, the complexes reported here are the first corroborative structural models of the Co(II)-substituted SOD.
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