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Schematic overview of the encryption and decryption of the macromolecular pin codes. a) The reversible TAD‐indole covalent bonds imbedded in the backbone of the pin codes enable cleavage of the digits upon heating. b) Upon cooling, the digits reconnect with one another in a random manner, thereby leading to a statistical mixture of unreadable oligomers. c) The encrypted pin code can only be decrypted upon subsequent heating in the presence of a trapping agent, which allows the monomer digits to separate from one another. d) The resulting mixture of monomers can eventually be read out via ESI‐MS analysis and their original order can be deciphered from the attached chemical fingerprints, hence revealing the initially written pin code.
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Dynamic sequence‐defined oligomers carrying a chemically written pin code are obtained through a strategy combining multicomponent reactions with the thermoreversible addition of 1,2,4‐triazoline‐3,5‐diones (TADs) to indole substrates. The precision oligomers are specifically designed to be encrypted upon heating as a result of the random reshuffli...
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Linear uniform oligomers synthesized via a two‐step iterative cycle are postmodified with uniform octaethylene glycol monomethyl ether and finally coupled via azide‐alkyne cycloaddition to yield uniform star‐shaped block macromolecules with a mass ranging from 10 to 14 kDa. Each of the molecules is carefully characterized by NMR, electrospray ioniz...
Citations
... Compared to ESI-MS, in which multiply charged species are overlaid and data interpretation is difficult, MALDI-TOF MS generates mostly singly charged species and affords cleaner MS patterns with excellent tolerance of contaminants and salts 30 . However, during the decoding of sequence-defined polymers, MALDI tandem MS patterns can be still complicated by non-specific bond cleavages and by charged molecular fragments from both sides of each chain fragmentation event 18,19,24,33,34 . Although the incorporation of labile linkages into polymers could enhance fragmentation selectivity, a delicate balance has to be ensured in our design to maintain the integrity of parent ions. ...
... Compared to inorganic NPs, for which well-established characterization techniques (elemental/nuclear analysis) and intrinsic imaging methods (magnetic resonance and optical imaging, positron emission tomography) exist 5 , the in vitro and in vivo tracking of polymeric NPs-which represent the vast majority of nanomedicines currently Compared to ESI-MS, in which multiply charged species are overlaid and data interpretation is difficult, MALDI-TOF MS generates mostly singly charged species and affords cleaner MS patterns with excellent tolerance of contaminants and salts 30 . However, during the decoding of sequence-defined polymers, MALDI tandem MS patterns can be still complicated by non-specific bond cleavages and by charged molecular fragments from both sides of each chain fragmentation event 18,19,24,33,34 . Although the incorporation of labile linkages into polymers could enhance fragmentation selectivity, a delicate balance has to be ensured in our design to maintain the integrity of parent ions. ...
... These GPC, NMR and MALDI data complementarily verified the successful synthesis of sequence-defined polymeric amphiphiles. [32][33][34]. For T-01001011-dPEG with discrete molecular weights, the MS peak is associated with doubly charged ions, and ESI tandem MS reveals quite complicated patterns due to the presence of multiply charged species and irregular fragmentation pathways ( Supplementary Fig. 33). ...
Identification and quantification of synthetic polymers in complex biological milieu are crucial for delivery, sensing and scaffolding functions, but conventional techniques based on imaging probe labellings only afford qualitative results. Here we report modular construction of precise sequence-defined amphiphilic polymers that self-assemble into digital micelles with contour lengths strictly regulated by oligourethane sequences. Direct sequence reading is accomplished with matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry, facilitated by high-affinity binding of alkali metal ions with poly(ethylene glycol) dendrons and selective cleavage of benzyl-carbamate linkages. A mixture of four types of digital micelles could be identified, sequence-decoded and quantified by MALDI and MALDI imaging at cellular, organ and tissue slice levels upon in vivo administration, enabling direct comparison of biological properties for each type of digital micelle in the same animal. The concept of digital micelles and encoded amphiphiles capable of direct sequencing and high-throughput label-free quantification could be exploited for next-generation precision nanomedicine designs (such as digital lipids) and protein corona studies.
... 25 In another example, Holloway et al. reported the use of ESI-MS and haolgen-based labels to identify the initial position of different monomer "digits" in thermoreversibly scrambled 1,2,4-trizoline-3,5dione-indole oligomers. 49 Building upon these previous works, as well as our own sequencing paradigm, we hypothesized it would be possible expand on isotopic labels previously used to differentiate sequence-defined oligomers in complex mixtures, and sort the oligomers according to these labels to store more significant amounts of information. ...
Molecular encoding in abiotic sequence-defined polymers (SDPs) has recently emerged as a versatile platform for information and data storage. However, the storage capacity of these sequence-defined polymers remains underwhelming compared to that of the information storing biopolymer DNA. In an effort to increase their information storage capacity, herein we describe the synthesis and simultaneous sequencing of eight sequence-defined 10-mer oligourethanes. Importantly, we demonstrate the use of different isotope labels, such as halogen tags, as a tool to deconvolute the complex sequence information found within a heterogeneous mixture of at least 96 unique molecules, with as little as four micromoles of total material. In doing so, relatively high-capacity data storage was achieved: 256 bits in this example, the most information stored in a single sample of abiotic SDPs without the use of long strands. Within the sequence information, a 256-bit cipher key was stored and retrieved. The key was used to encrypt and decrypt a plain text document containing The Wonderful Wizard of Oz. To validate this platform as a medium of molecular steganography and cryptography, the cipher key was hidden in the ink of a personal letter, mailed to a third party, extracted, sequenced, and deciphered successfully in the first try, thereby revealing the encrypted document.
... anticounterfeiting, macromolecular data storage). [27,28] A chemical platform that enabled the synthesis of sequence-encoded macromolecules susceptible towards ondemand chemical degradation was developed by introducing esters in the backbone of the macromolecules. While esters are generally regarded as being bench-stable, they can be readily hydrolysed upon exposure to specific conditions (e.g. ...
Sequence‐defined polymers have been the object of many fascinating studies that focus on their implementation in both material and life science applications. In parallel, iterative synthetic methodologies have become more efficient, whereas the structure elucidation of these molecules is generally dependent on MS/MS analysis. Here, we report an alternative, simple strategy for the determination of the monomer order of uniform oligo(thioether ester)s. This approach, which relies on random cleavages of ester units within the macromolecular backbone via a basic treatment, enables the swift characterization of these macromolecules without the need for MS/MS. Consequently, this method can be used for decoding any information stored within the primary structure of oligoesters by means of ESI‐ or LC–MS. Finally, we speculate that a range of structurally diverse backbones could be susceptible towards this approach, which could promptly expand the library of chemically sequenceable macromolecules.
... [19] Using an analogous concept, our research group incorporated dynamic covalent bonds in the backbone of information-containing macromolecules. [20] This feature allowed to scramble the stored data, after which it could only be decoded using the correct pin code. Nonetheless, features such as erasing or scrambling are mainly interesting when targeting anti-counterfeiting applications, yet provide little to no added value for the long-term storage of information. ...
Rewriting data stored on synthetic macromolecules is an interesting feature, even though it is considered as being quite challenging within the area of digital macromolecules. In this context, we initially studied a strategy for modifying the position tag of sequence‐encoded macromolecules in a reversible manner. The efficiency of this method, which relies on the orthogonal cleavage of a thioester moiety via aminolysis, was demonstrated by modifying parts of an exemplary sentence. Simultaneously, a novel algorithm was developed to ease the read‐out of macromolecular information by means of MS/MS techniques. This program, Oligoreader, can identify potential information‐containing macromolecules from a series of MS¹ spectra, analyze the corresponding MS² spectra, and finally decode the data. Consequently, the algorithm simplifies the entire read‐out process by avoiding any interference from the operator, which increases the potential for blind sequencing of uniform macromolecules.
... Taking surface chemistry and advanced characterization, onsurface electrosynthesis of single and insoluble polymers with high molecular weight can be expected. With electrochemical features and advanced interdisciplinary research, we envisage that controlled electropolymerization as a new concept can join the forefront of polymer science and contribute to advanced polymer chemistry and materials for refreshing or replacing applications such as catalysis [47], digital memory [48], information storage [49], and molecular electronics [50,51] based on multilayers and monolayers of polymers. Studies on these applications are currently ongoing in our laboratory. ...
Electropolymerization is one of the most important methodologies to synthesize and develop conducting polymers. The complexity of the polymerization mechanism, ion doping processes and structural defects are considered to be symbiotic and unavoidable, making the stagnant state and huge band gap with advanced interdisciplinary research fields and important applications in the last three decades. Herein, we provide a point of view into controlled electropolymerization by regioselective activation reactions of monomers, where self-dimerizations instead of self-electropolymerizations were utilized. The resulting dimers play a role in the connections between functional building blocks to form functional polymers on demand. This account highlights the typical findings in controlled electropolymerizations as a forum for discussing new opportunities in exploiting novel designs and applications.
... In the beginning, scientists mainly focussed on the synthesis of these highly complex structures and developed various different strategies towards uniform molecules. A lot of different synthetic pathways have been developed in the meantime, whereby an increasing degree of control and precision was achieved [2][3][4][5][6][7][8][9][10][11][12] . Iterative approaches are commonly used to synthesize sequence-defined molecules, since the molecules are formed step-by-step, thus enabling the highest possible control over the monomer units 6,9,[13][14][15][16][17][18] . ...
... For example, Du Prez et al. reported the use of ESI-MS for a successful read-out 2 . Until now, only a limited number of sequencedefined oligomers have been applied for the application in data storage 2,3,5,[36][37][38][39][40][41] . The number of selectable functional groups per repeating unit is important for molecular data storage, as it defines the achievable number of permutations and thus the storage capacity. ...
In recent years, the field of molecular data storage has emerged from a niche to a vibrant research topic. Herein, we describe a simultaneous and automated read-out of data stored in mixtures of sequence-defined oligomers. Therefore, twelve different sequence-defined tetramers and three hexamers with different mass markers and side chains are successfully synthesised via iterative Passerini three-component reactions and subsequent deprotection steps. By programming a straightforward python script for ESI-MS/MS analysis, it is possible to automatically sequence and thus read-out the information stored in these oligomers within one second. Most importantly, we demonstrate that the use of mass-markers as starting compounds eases MS/MS data interpretation and furthermore allows the unambiguous reading of sequences of mixtures of sequence-defined oligomers. Thus, high data storage capacity considering the field of synthetic macromolecules (up to 64.5 bit in our examples) can be obtained without the need of synthesizing long sequences, but by mixing and simultaneously analysing shorter sequence-defined oligomers.
... Following an exciting approach to develop rewritable polymer brush micropatterns [223] , very lately, a commendable work has been successfully carried out based on TAD-indole covalent 'click' and P3CR reactions in synthesizing dynamic sequencedefined polymers to generate macromolecular pin codes for anticounterfeiting purposes [224] . Polymer-based banknotes commonly contain highly secured ever-changing layers of printing to shield against counterfeiting activities. ...
... Polymer-based banknotes commonly contain highly secured ever-changing layers of printing to shield against counterfeiting activities. Holloway et al. [224] exploited TAD derived dynamically 'clicked' sequence-defined encrypted oligomers to add hidden chemical labels onto the surface of polymeric banknotes. Initially, TAD 'clicked' sequence-defined oligomer (A-B-C-D, Scheme 32 ) was encrypted by heating (in the absence of any 'transclick' agent, e.g., HDEO) at 120 °C for 2 h in butyl acetate, and re-dissolved in a minimum volume of ethanol (a nontoxic solvent) at r.t. and deposited on a biaxially oriented surface of polypropylene banknotes. ...
... Decryption of a encrypted sequence-defined oligomer ( A-B-C-D ) code using HDEO via 'transclick' chemistry.[224] Copyright 2020, Adapted with permission from John Wiley and Sons Inc. ...
It has been almost two decades since the concept of ‘click’ chemistry was anchored in the monumental field of chemistry. Later, numerous chemical approaches have been implemented that exhibit features kindred to ‘click’ chemistry toolbox. Unlike the synthesis of organic compounds involving typical purification procedures, the modular and orthogonal ‘click’ concept substantially embraces the material research community with delineating innumerable macromolecular architectures. In polymer chemistry, there are various types of ‘click’ reactions like copper (I) catalyzed alkyne-azide (CuAAC), strain promoted alkyne-azide cycloaddition (SPAAC), Diels-Alder, Alder-ene, thiol-ene, thio-bromo, etc., are used to prepare different functional polymers. Among the various ‘click’ reactions, recently, the ultrafast ‘click’ modification based on different 1,2,4-triazoline-3,5-dione (TAD) derivatives has gained tremendous attention in the broad platform of polymer research. Similar to singlet oxygen, the heterocyclic TAD reagents undergo ‘click’ conjugation within a concise timescale. Following the uncovering of the conventional routes for synthesizing TADs, few spellbinding categories of research have been carried out to develop different functional polymers for diverse applications. The perspective of this review is to cover the recent fascinating outcomes from TAD based ultrafast ‘click’ modification of macromolecules. This review highlights the present state-of-the-art of synthesis of new TAD molecules and their use in designing different macromolecular systems with remarkable features based on ultrafast TAD ‘click’ chemistry.
Precise sequence‐defined polymers (SDPs) with uniform chain‐to‐chain structure including chain length, unit sequence, and end functionalities represent the pinnacle of sophistication in the realm of polymer science. For example, the absolute control over the unit sequence of SDPs allows for the bottom‐up design of polymers with hierarchical microstructures and functions. Accompanied with the development of synthetic techniques towards precision SDPs, the decoding of SDP sequences and construction of advanced functions irreplaceable by other synthetic materials is of central importance. In this Minireview, we focus on recent advances in SDP sequencing techniques including tandem mass spectrometry (MS), chemically assisted primary MS, as well as other non‐destructive sequencing methods such as nuclear magnetic resonance (NMR) spectroscopy, circular dichroism (CD), and nanopore sequencing. Additionally, we delve into the promising prospects of SDP functions in the area of cutting‐edge biological research. Topics of exploration include gene delivery systems, the development of hybrid materials combining SDPs and nucleic acids, protein recognition and regulation, as well as the interplay between chirality and biological functions. A brief outlook towards the future directions of SDPs is also presented.
Precise sequence‐defined polymers (SDPs) with uniform chain‐to‐chain structure including chain length, unit sequence and end functionalities, represent the pinnacle of sophistication in the realm of polymer science. For example, the absolute control over the unit sequence of SDPs allows for bottom‐up design of polymers with hierarchical microstructures and functions. Accompanied with the development of synthetic techniques towards precision SDPs, the decoding of SDP sequences and construction of advanced functions irreplaceable with other synthetic materials is of central importance. In this Minireview, we focus on recent advances in SDP sequencing techniques including tandem mass spectrometry (MS), chemically assisted primary MS, as well as other non‐destructive sequencing methods such as nuclear magnetic resonance (NMR) spectroscopy, circular dichroism (CD), and nanopore sequencing. Additionally, we delve into the promising prospects of SDP functions in the area of cutting‐edge biological research. Topics of exploration include gene delivery systems, the development of hybrid materials combining SDPs and nucleic acids, protein recognition and regulation, as well as the interplay between chirality and biological functions. A brief outlook towards the future directions of SDPs is also presented.
