Modeling and theoretical analysis of ring specific mimicry in view of isomerism within medicinal promising oligomers of "DIVEMA"

   
Bolshchikov B.D.1, Tsvetkov V.B.2, Alikhanova O.L.3, Serbin A.V.3

1. Topchiev Institute of Petrochemical Synthesis, RAS, Moscow, Russia
2. Research Center for Biomodulators, Health Research and Development Foundation, Moscow, Russia
3. Topchiev Institute of Petrochemical Synthesis, RAS, Moscow, Russia; Research Center for Biomodulators, Health Research and Development Foundation, Moscow, Russia
Section: Bioinformatics and Chemoinformatics
DOI: 10.18097/PBMC20196502133      PubMed Id: 30950818
Year: 2019  Volume: 65  Issue: 2  Pages: 133-151
The furan or pyran related hetero cycles play basic role in structural units of nucleic acids (NA) and polysaccharides (PS), significantly predetermining their functional specifics. Some of such properties, in great relevancy for medicine, can be imitated through mimicry of polymers synthetic. Particularly, a formation of similar cycloisomeric chains is possible in process of free-radical cyclocopolymerization of divinyl ether (DVE) and maleic anhydride (MA). The products yielded (DVEMA) of general formula [DVE(MA)-alt-MA]n become precursors for a broad family of water-soluble derivatives capable of wide spectrum of bioactivity, including induction of interferon, immune-stimulated and direct antiviral protection. In this connection, the knowledge: what is content of different heterocyclic isomers in backbone of the preparations and what their partial contributions in promotion of the certain bioactivities observed, are in great importance. Available experimental data (NMR, IR, etc.), controversial for interpretations, didn't elucidate a required estimation of the DVEMA isomerism. The current work represents an independent exploration of the problem via quantum chemistry-based analysis of kinetic (activation barriers) and thermodynamic (enthalpies) priorities in competition between variable isomerism within the chain synthesis. The system is considered in maximal range of hypothetically allowable variations of two levels for double regioselective bifurcations: there are four competitive ways, each of which involves a sequence of four type elementary reactions for a diverse-isomeric formation of chain units. A genesis of six chiral centers (62 stereoisomers permitted) per every of the four part ways was accounted in view for up to 256 isomeric variations in total. The required time-minimized but precisely accurate computations were conducted via B3LYP/6-31G(d), M06-2X/6-311+G(d), M06-2X/6-31+G(2df,p) techniques, which were preselected through model test-systems. As a result, the mechanisms, crucial points and factors for the process-permitted regulation of isomeric content of DVEMA were studied in details. The narrow enough set of most probable enantiomers within highly competitive 5-exo- and 6-endo- ring closing sub-ways was revealed. The results obtained are very actual for an adequate modeling (docking / molecular dynamics) of DVEMA derivatives in their interactions with biopolymer targets, in search for purposed advancement of current background in design and synthesis of highly effective agents for combined antiviral protection (against HIV, flu, herpes, and other infections).
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Keywords: polymerization, cyclization, isomerism, biological activity, modeling, DIVEMA
Citation:

Bolshchikov, B. D., Tsvetkov, V. B., Alikhanova, O. L., Serbin, A. V. (2019). Modeling and theoretical analysis of ring specific mimicry in view of isomerism within medicinal promising oligomers of "DIVEMA". Biomeditsinskaya khimiya, 65(2), 133-151.
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