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

Abstract

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 CF3‐substituted cycloalkyne IC9O‐CF3.

Synthesis of Substituted Triazole-Pyrazole Hybrids using Triazenopyrazoles Precursors

“…[1,2] We were interested in feasible strategies to synthesize nitrogen-rich heterocyclic scaffolds that can extend the currently available libraries with new drug-like molecules. Our past work on pyrazoles [3][4][5][6] and triazoles [7][8][9][10][11] motivated us to search for suitable and versatile strategies to explore access to triazole-pyrazole hybrids. Triazole-pyrazole hybrids, particularly non-fused heterocycles of this class, have not been investigated systematically.…”

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

“…We are interested in feasible strategies to synthesize nitrogen-rich heterocyclic scaffolds that can extend the currently available libraries with new drug-like molecules. Our past work on pyrazoles [3][4][5][6] and triazoles [7][8][9][10][11] motivated us to search for suitable and versatile strategies to explore access to triazole-pyrazole hybrids. Triazole-pyrazole hybrids, particularly non-fused heterocycles of this class, have not been investigated systematically.…”