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DNA mimetics: Synthetic molecular duplexes

Periodic Reporting for period 1 - DNAmics (DNA mimetics: Synthetic molecular duplexes)

Reporting period: 2016-01-01 to 2017-12-31

One of the main unanswered challenges of modern science is how to control macroscopic properties of known materials at molecular level. In order to achieve this task it is of crucial importance to know how molecules assemble and form aggregates, that is to understand how molecules interact. Despite significant scientific advances in last decades precision and predictability of assembly of non-natural building blocks is significantly lagging behind natural systems. Nature uses sequences of monomers (peptides, nucleic acids) to guide and control assembly. In other words, nature uses information in form of sequence of connected building blocks to program the assembly, and consequently arranges non living material into biological systems. Moreover, DNA base pairing was chosen as nature's way of storing, copying and reading genetic information and driving the evolution. Only recently DNA is used to program the assembly outside the cell, and to form functional and novel materials.
However, despite attractiveness and availability,the DNA is perfected to work in an aqueous environment, and as such it is difficult to make it work in non water soluble media, which is majority of materials. Hence, using nature's strategy, and bottom up preparation of non-natural sequences of recognition sites should combine the best of both worlds. Hence, information molecules consisting of sequences of hydrogen bond donor and acceptor sites were prepared. To test reliability and fidelity of recognition of complementary strands, binding was quantitatively determined by using nuclear magnetic resonance or thermal methods. Overall objective of designing and preparation of artificial sequences of recognition sites, capable of recognition of complementary sequences is fulfilled, which is essential for further use and application of such a molecules.
Prepared sequences can be easily used with know polymers to form new materials with unprecedented mechanical, electronic or photochemical properties. Formation of self-healable thermoplastic elastomers, size controllable nanoparticles for drug delivery, or materials with controllable microphase separations for electronic devices can be envisaged. Above mentioned, are all materials that will are expected to be the basis for the future, and prospherity of knowledge based society.
During the reporting protocol three main objectives were achieved. First objective was to design and prepare molecules that are capable of storing information in form of sequence of recognition sites. In other words, the goal was to obtain molecules that will complement natural counterparts, namely the DNA, in apolar media. For that matter, melamine core was used as backbone, due to stability and robustness of the chemistry used to obtain it. Hence, information oligomers were obtained in high yields. Second objective was to test molecular recognition between complementary strands. By synthesizing all sequences of dimer and trimer information oligomers, as part of first objective, interactions of complementary strands were measured. The results show that there is cooperative binding between complementary strands. Cooperativity is evident in both different lengths of oligomers, as well as different complementary sequences. From performed experiments it was evident that duplex between complementary recognition sequences was achieved with high stability and in cooperative manner. Also, intramolecular hydrogen bonding was not observed, which is crucial for formation and stability of duplexes. Furthermore, imperfections in duplex formation were explored by investigating duplex formation by non-complementary sequences. It is evident that non-complementary sequences form less stable duplexes than complementary ones, which indicates high fidelity in recognition and reading of information by complementary sequence. Experiments showing that tempting by can be achieved in tetramer templated oligomerisation, indicating that copying of information in prepared systems is possible.

Overall, all objectives were achieved. Completely artificial system, that stores information as sequence of recognition sites was obtained. Reliability of forming duplexes with complementary strands, was measured. Also imperfections due to recognition on non-complementary strands were explored. In total, artificial system that is capable of storing, reading and copying sequence information is developed. This system shows great promises as scaffold for obtaining new smart materials with capabile of memory storage, self healing, and evolving properties.

Obtained results were presented at international conferences, and symposium, either as oral or poster presentations. The overview and results of the project are visible on supplied web address, and are publicly available to any interested reader. Initial results of the project were presented at Open Days in the Department of Chemistry, University of Cambridge, to high school, undergraduate, and master students, as well as PhD candidates. Results of the project, were presented at international conferences in Switzerland, UK, and USA, to scientific community as invited oral and/or poster presentations.
Performed research was envisaged to bridge the gap between biological and synthetic systems, by potentially combining properties of both. Designed and achieved system is the first fully functional system capable of mimicking functions of nature's greatest feat, the DNA. Modular design achieved in this project, has high value due to two facts. First in this project it was verified that is fully functional, and capable of storing, reading and copying information stored as a sequence of recognition sites. Second, since design is highly modular every element can be exchanged and specifically incorporated for specific function and environment. Since recently, reliability of DNA base pairing has been widely used in formation of smart materials. Proposed system could complement and in many instances surpass, nature's buiding block. Namely, prepared information oligomers are compatible with known polymeric materials, and are designed to work in non polar medium. Hence, combining them with known polymers, self healable materias, single chain nanoparticles with programmable folding or microphase separated polymers for electronic devises can be prepared. Moreover, since prepared molecules are bench stable oligomers, by creating longer oligomers high density memory storage devices are potentially obtainable.
Overall, prepared molecules present new class of compounds, that can be used in preparation of smart materials, which will be foundation of knowledge based society.
Structural blueprint of designed molecules
Main objectives for artificial information oligomers