Subject of investigation: topological and conformational factors of functioning of macroheterocycles in the processes of complexation, isotope and enantiomers separation, suppression of tumours and microorganisms growth. Target of investigation: To discover common regularities of the macroheterocycles topology and geometry influencing on the features of their functioning as selective complexones, enantiodifferentiating agents, and also antineoplastic, antiviral and antimicrobial remedies. To develop approaches and methods for prediction and design of macroheterocyclic compounds with the complex of the preset properties. Methods of investigation and instruments: topological analysis of the molecular graphs of macroheterocycles (MHC); harmonic analysis of the conformations of MHC; molecular mechanics; barycentric coordinate method; penalty function method; saddle nodes localization и and search of the ways of the least energy on the potential surface of MHC method; quantitative estimation of chirality power, stereoanalysis and stereodesign of chiral MHC; molecular design of supramolecular macroheterocyclic compounds; simplex representation of molecular structure; regression analysis, partial least squares (PLS), and answer trees methods. Theoretical results and novelty: Conception of "topological effect of complexation" has been suggested. Such effects as macrocyclic, polychelate, criptand, etc. have been generalized and united by it. Specialized topological index has been developed. It allows estimating "topological effect of complexation" quantitatively. The design of perspective polidentate ligands in which the topology of donor centers jointing provides effective complexation with cations of metals. It was shown, that Fourier transformation of the geometrical parameters of MHC allows systematizing of possible conformation transformations, estimating realization of chiral conformer's possibilities, relative conformation lability of macrocycles and degree of structural similarity for different conformers.In the framework of the given approach the degrees of deformation of crown ether cycles under the influence of different cations were compared. Geometrical descriptions allowing to describe such features of shape of cycle, as "sphericity", "convexification" and angular "folding" has been suggested. Generation of the initial approaching method for the for the searching of local minimums on the potential surfaces of macrocyclic molecules has been developed. Dependence of the MHC complexation with different cations selectivity from the size of macrocycle, donor centers, structural "rigid" fragments (benzo and cyclohexane crown ethers) and substitutients in macroheterocycle amount and relative position, and also presence or absence of donor centers in the last ones has been explored systematically. The trajectories of interaction ion - ligand in situation when the conformation transformation of ligand under the influence of cation be the the limiting stage of complexation (Eigen-Winkler mechanism) have been investigated using the search method of saddle points and ways of the least energy on the potential surface of molecule. Principle possibility of isotopes separation for alkaline metals cations by crown-ethers in the conditions of kinetic control of complexation was shown. The conception of "kinetic macrocyclic effect" was formulated and the possibilities of its realization were explored. Methods of dissymmetry and asymmetry functions for quantitative estimation of not only chirality of molecules but also "quasisymmetry" in relation to any elements of point symmetry groups has been developed. The new, more universal formulation of concept of stereochemical configuration has been offered on the base of the simplex representation of molecular structure. Procedure of stereoanalysis, which allows defining the stereochemical configuration of any chiral structure, expressing the last one as a stereochemical code, has been developed. Concept of atom "stereochemical charge" and "stereochemical moment" of molecule has beenentered. Possibility of determination for "topiсity" atoms in a molecule on the basis of analysis of their stereochemical charges was shown. The theoretical analysis of stereodifferentiating ability for chiral crown derivatives of D - tartaric acid has been elaborated. Structural factors determining the ability of these ligands for the separation of enantiomer "guests" has been discovered. The ways of structural modification of intrinsic chiral para-substituted calyx[4]arenes, providing maximal chirality of ligand cavity has been determined. Conception of "chirality translation in spaces of a different dimension" has been formulated. On this base the general principles of absolute asymmetric synthesis of chiral molecules, for example, calyxarenes has been offered. The molecular design of spiral-organized columnar anisotropic mesophase from symmetric (C4) chiral calyxarenes has been elaborated and it has been demonstrated how to construct ligands for the separation of enantiomeric fullerenes with the chiral frame on the basis of these synthones. The molecular design technology of supramoleculyar compounds, based on "assembling" of synthetic receptor from molecular blocks on the matrix of "guest", has been developed. Mentioned approach allows constructing a new type of macrocyclic ligands - "braceletands" and offering the ways of the structural adjusting of complexation selectivity such ligands with cations of different metals. Within the framework of different 2D - 4D QSAR models the influence of macrocyclic piridinophanes and their analogues (more than 60 connections) structure on their antitumor and antiviral activity, and influence of various crown ethers (more than 200 connections) structure on their antimicrobial activity has been investigated. The structural fragments of molecules, most affecting the studied properties, have been exposed for all tasks. New compounds with the high level of predicted antitumor and antiviral activity has been designed. In a number of cases this activity values has been confirmed experimentally. Practical results and novelty: The obtained in the given work results are determine the ways of purposeful creation of new macroheterocyclic ligands for the effective separation of cations of metals (including isotopes) and enantiomeric "guests". It was shown, how it is necessary to modify the MHC structure for creation on their basis new antitumor, anti-viral and antimicrobial remedies. The developed methods and approaches having a universal character and are suitable for the decision of the most various tasks "structure - properties". In particular, from results not entering in the given dissertation, it is possible to mark quantitative relationship between a structure and mesomorphic properties of molecules, odorant activity for heterocycles set, luminescent properties of diketonates rare earth elements, reaction ability of substituted diethylmalonates, catalytic activity of 3d metals polinuclear carboxylates in the reactions of liquid-phase oxidation. For the decision of all mentioned tasks the complex of the computer programs, allowing carry out the topological and conformational analysis of molecules, authentication of their stereochemical configuration and estimation of measure of chirality, construction of dependences "structure - properties" has been created. The set of developed in the given work conceptions has been entered in the special courses "Design and analysis of molecular structure", "Drug Design", "Molecular morphometrics". All of them an author reads to the students of chemical department of the I.I. Mechnikov Odessa National University. Subject and degree of introduction: publications, lectures at scientific conferences, usage of given results in scientific-pedagogical practice of Institutes of Ukraine. Efficiency of introduction is provided by development of approaches for the analysis of structure influence on properties of macroheterocycles and methods of the new compounds with the complex of useful properties constructing. Field of application: chemistry and medicine.
