title: Thermodynamic and structural aspects of novel 1,2,4-thiadiazoles in solid and biological mediums.
abstract: Novel 1,2,4-thiadiazoles were synthesized. Crystal structures of these compounds were solved by X-ray diffraction experiments, and comparative analysis of packing architecture and hydrogen bond networks was carried out. Thermodynamic aspects of sublimation processes of the compounds under study were analyzed using temperature dependencies of vapor pressure. Thermophysical characteristics of the molecular crystals were obtained and compared with the sublimation and structural parameters. The melting points correlate with sublimation Gibbs energies. Moreover, an increase of donor-acceptor interactions in crystal structures leads to growth of Gibbs energy values. Relationships between the melting points and the fragmental contributions to the packing energies were established: R(1)-R(4) fragmental interactions are responsible for the fusion processes of this class of compounds. Solubility and solvation processes of 1,2,4-thiadiazoles in buffer, n-hexane and n-octanol were studied within a wide range of temperature intervals, and their thermodynamic functions were calculated. Specific and nonspecific interactions of molecules resolved in crystals and solvents were estimated and compared. It was found that the melting points correlate with sublimation Gibbs energies. Distribution processes of compounds in buffer/n-octanol and buffer/n-hexane systems (describing different types of membranes) were investigated. Transfer processes of the studied molecules from the buffer to n-octanol/n-hexane phases were analyzed by the diagram method with evaluation of the enthalpic and entropic terms. This approach allowed us to design drug molecules with optimal passive transport properties. Calcium-blocking properties of the substances were evaluated. The trend between the ability to inhibit Glu-Ca uptake and the distribution coefficients in buffer/hexane system was observed.
authors.affiliation: Institute of Solution Chemistry, Russian Academy of Sciences, 153045 Ivanovo, Russia. glp@isc-ras.ru
authors.forename: German L
authors.initials: GL
authors.lastname: Perlovich
authors.forename: Alexey N
authors.initials: AN
authors.lastname: Proshin
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Volkova
authors.forename: Cong Trinh
authors.initials: CT
authors.lastname: Bui
authors.forename: Sergey O
authors.initials: SO
authors.lastname: Bachurin
mesh_terms: D000465:Algorithms; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology*; D055598:Chemical Phenomena; D015195:Drug Design; D018698:Glutamic Acid / Q000378:metabolism; D055595:Mechanical Phenomena; D008958:Models, Molecular; D008968:Molecular Conformation; D014179:Neurotransmitter Uptake Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013816:Thermodynamics; D013830:Thiadiazoles / Q000737:chemistry* / Q000494:pharmacology*; D014867:Water / Q000032:analysis
chemical_list: D002121:Calcium Channel Blockers; D014179:Neurotransmitter Uptake Inhibitors; D012997:Solvents; D013830:Thiadiazoles; D014867:Water; D018698:Glutamic Acid; D002118:Calcium