Development of Fluorescent Isocoumarin‐Fused Oxacyclononyne – 1,2,3‐Triazole Pairs

Fluorescent isocoumarin-fused cycloalkynes, which are reactive in SPAAC and give fluorescent triazoles regardless of the azide nature, have been developed. The key structural feature that converts the non-fluorescent cycloalkyne/triazole pair to its fluorescent counterpart is the pi-acceptor group (COOMe, CN) at the C6 position of the isocoumarin ring. The design of the fluorescent cycloalkyne/triazole pairs is based on the theoretical study of the S1 state deactivation mechanism of the non-fluorescent isocoumarin-fused cycloalkyne IC9O using multi-configurational ab initio and DFT methodologies. The calculations revealed that deactivation proceeds through the electrocyclic ring opening of the α-pyrone cycle and is accompanied by a redistribution of electron density in the fused benzene ring. We proposed that the S1 excited state deactivation barrier could be increased by introducing a pi-acceptor group into a position that is in direct conjugation with the formed C=O group and has a reduced electron density in the transition state. As a proof of concept, we designed and synthesized two fluorescent isocoumarin-fused cycloalkynes IC9O-COOMe and IC9O-CN bearing pi-acceptors at the C6 position. The importance of the nature of a pi-acceptor group was shown by the example of much less fluorescent CF$_3$-substituted cycloalkyne IC9O-CF$_3$

Hemostasis protein-coding genes, peripheral hemostasis parameters, and atherothrombosis predisposition in patients with cardiovascular disease

Aim. To study the associations between polymorphic variants of hemostasis protein-coding genes, hemostasis system functioning, and atherothrombosis development in patients with cardiovascular disease (CVD). Material and methods. The study included 76 patients. Polymorphic gene marker alleles were analyzed by PCRPDRF method. Results. The genotype prevalence was assessed for the polymorphic variants of F V, F II, Gp Iα, Gp IIIα, Gp Iβα, PAI-1, and FBG genes. In CVD patients, a polymorphic variant 4G (-675)5G of PAI-1 gene was associated with peripheral hemostasis disturbances. Conclusion. 5G allele of PAI-1 gene was associated with higher plasminogen concentration and lower PAI-1 levels, which resulted in reduced plasma thrombogenicity

Electrophilic Cyclization of Aryldiacetylenes in the Synthesis of Functionalized Enediynes Fused to a Heterocyclic Core

An efficient strategy for the synthesis of asymmetrically substituted enediynes fused to benzothiophene, benzofuran, and indole was developed. The proposed approach is based on the electrophilic cyclization of diacetylenes and Sonogashira coupling. Thus, iodocyclization of readily available <i>ortho</i>-functionalized (buta-1,3-diynyl)­arenes was used as a direct way for the synthesis of 2-ethynyl-3-iodoheteroindenes. These substrates and their modified derivatives were easily converted by Sonogashira coupling with acetylenes to a variety of asymmetrically substituted acyclic enediynes fused to heterocycles. The tolerance of the developed methodology to a variety of functional groups is a great advantage in the synthesis of macrocyclic enediyne systems fused to a heterocyclic core. Synthesis of indole-fused 12-membered macrocyclic dienediyne was achieved using ring-closing metathesis as a key step