1 H NMR studies of 1 þ equimolar dAMP versus time. 

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... order to test this hypothesis the reaction of deoxyadenosine monophosphate (dAMP) with 1 was studied. The 1 H NMR of equimolar amounts of dAMP and 1 in D 2 O was followed over a 24 h period using water suppression. Although evidence of reaction is observed in the form of new resonances appearing in the down fi eld (8 ppm) and up fi eld (2 e 7 ppm) regions of the spectrum the H(8) of the adenine is still present after 24 h ( Fig. 4). Thus the reaction 1 with dAMP is much slower than with dGMP and appears to be less speci fi c, given the greater number new resonances that appeared over the 24 h period. Nonetheless, this experiment does lend credence to the idea that the outlier labels (red dots) are 1-dAMP although it is not clear if this product has the same structure as 1 - dGMP (Equation (2)). Monofunctional Pt complexes give simpler Pt-G monoadducts. N7 of both adenine and guanine can be platinated, however N7 of guanine shows a greater kinetic preference. This tendency results from the stronger basicity of that nitrogen and from possible simultaneous hydrogen-bond interactions between NH þ 3 protons and the O(6) of guanine. In contrast, in the case of adenine, only repulsive interactions can be produced between the NH 2 in position 6 of adenine and a platinum-bonded amine ligand [9]. The TEM experiment constitutes a proof of concept in that it illustrates that it is possible to visualize a single platinum atom with base selectivity, bound to stretched single-stranded DNA. However, for this labeling scheme to be effective the reaction of 1 with dGMP must be much faster. To this end, a study of the rates of reaction of a series of complexes related to 1 , Pt(en)Cl(NH 2 R)] þ NO 3 where R ] C 8 H 11 N (phenethylamine) ( 2 ), C 7 H 9 N (benzylamine) ( 3 ), C 6 H 7 N (aniline) ( 4 ), C 6 H 6 IN ( p -iodo-aniline) ( 5 ) C 3 H 9 NO (2-methoxy-eth- ylamine) ( 6 ) and C 6 H 13 N (cyclohexylamine) ( 7 ) were synthesized and their rates of reaction with dGMP were followed by 1 H NMR (Chart 1). The amines were chosen for their differences in steric bulk and basicity of the donor atom. The aromatic amines in this series were chosen based on the prior work of Heetebrij et al. who found that aromatic amines showed a higher af fi nity for guanine relative to the other bases and attributed this to p -stacking effects [9]. The aliphatic amines used were chosen for comparison to see how important the stacking effect was for the rate of reaction as well as the selectivity. In the case of 5 a second heavy atom was included to increase electron scattering to improve visualization of the label. The experiments were conducted with equimolar amounts of the amine complexes and dGMP in D 2 O with water suppression. The reaction of 2 with dGMP is shown in Fig. 5 and it can be seen that it reacts much more quickly 1 , with the reaction being almost complete after just 2 h. Fig. 6 compares the rate of conversion of 1 with 2 and 4 . Complex 3 showed the same rate of conversion as 1 , both being benzyl amines. Fig. 7 compares the rate of conversion of 4 with 5 and shows that inclusion of the iodine atom does not have huge in fl uence on the initial rate but does decrease the overall % conversion after 24 h. Complexes 6 and 7 reacted only sluggishly with dGMP and showed < 50% after 24 h. It is clear from these results that the longer tether in the phenethylamine complex results in the fastest rate of conversion and represents the best candidate for single metal atom labeling of guanine in single-stranded DNA. The studies with complexes 1 e 5 showed that a two-carbon tether gave the best rate of conversion. However, visualizing a single heavy metal atom label would require the very powerful TEM located at ORNL [11]. In the hope of combining the effectiveness of the two-carbon tether with a metal cluster label, which would allow in-house imaging with more conventional TEM instruments, we synthesized the compound [Os 3 (CO) 11 PPh 2 (CH 2 ) 2 NH 2 (en)PtCl] NO 3 ( 9 ) using the bidentate ligand 2-diphenylphosphino-ethyl- amine (Scheme 1). Os 3 (CO) 11 (CH 3 CN) [12] was reacted with 2- diphenylphosphino-ethylamine at ambient temperature in methylene chloride. The spectroscopic data indicated that the reaction had resulted in the displacement of a carbonyl ligand to give [Os 3 (CO) 10 PPh 2 (CH 2 ) 2 NH 2 ] ( 8 ) (Scheme 1). However, we could not determine if the ligand was coordinated in a bridging or chelating mode and so a solid-state structure was undertaken. The solid-state structure of 8 is shown in Fig. 7 with selected bond lengths and angles in the fi gure caption. The crystal and collection data are given in Table 1. The 2-diphenylphosphino-ethylamine ligand is chelated to one Os atom. There is considerable precedent in the literature for the chelate structure being preferred for bidentate ligands with an ethylene bridge in the chemistry of triosmium clusters. However, the equilibrium between the chelate and two metal atom bridging structure is highly dependent on the nature of the of the two ...