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The heteroatom nature in 10‐membered enediynes plays a crucial role in tuning of their reactivity in the Bergman cyclization, which is a decisive factor for the biological activity of enediynes. Although benzothiophene‐fused O‐ and N‐enediynes have been identified as promising biological objects, the corresponding thiaenediyne remains unknown. To fill this gap, we synthesized the thiaanalog and studied it in both practical and theoretical terms. While the Nicholas reaction has proven to be an effective cyclization technique for the preparation of heteroenediynes, in the case of thiaenediyne it was accompanied by an unusual acid‐promoted intramolecular cyclization, forming a thiepinium salt. The S‐enediyne has reduced reactivity in the Bergman cyclization relative to the N‐ and O‐enediynes, attributed to the diminished alkyne bending and extended cd‐distance. The NBO analysis of the entire series, namely the evaluation of πin/out(C2‐CC)→σ*(C−X) hyperconjugation, revealed that the S atom in S‐enediyne provides stronger stabilization of the initial compound than the N atom in N‐enediyne, while exhibiting the weakest stabilization of the Bergman cyclization transition state. NICS values were employed to examine the change in aromaticity along the Bergman cyclization coordinate. This approach, in conjunction with the NBO analysis, provides a foundation for further rational design of unnatural enediynes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article in the European Journal of Organic Chemistry discusses the synthesis and reactivity of a new member of the heteroenediyne group called thiaenediyne, obtained through Nicholas cyclization. Thiaenediyne is found to be the least reactive in the Bergman cyclization, highlighting the importance of the heteroatom in the enediyne moiety for the reactivity of enediynes in this process. The study also applies NBO analysis to benzothiophene‐conjugated heteroenediynes. For more information, readers can refer to the Research Article by I. A. Balova and co‐workers. [Extracted from the article]

A simple, efficient and atom-economic method has been developed for the synthesis of complex alkaloid-like compounds with spiro-fused indolo[2,1-b]quinazoline and cyclopropa[a]pyrrolizine or 3-azabicyclo[3.1.0]hexane moieties. We have found that one-pot, threecomponent 1,3-dipolar cycloaddition reactions allow the desired products to be obtained from various cyclopropene derivatives with tryptanthrin-derived azomethine ylides generated in situ, in good to high yields and excellent diastereoselectivity. The possibility of ylide generation was exemplified by using α-amino acids (L-proline, L-4-thiazolidincarboxylic acid) and simplest peptides (dipeptide Gly-Gly, tripeptide Gly-Gly-Gly). Quantum chemical investigations indicate that the reaction proceeds through the S-shaped azomethine ylide, the interaction of which with cyclopropenes proceeds via a less sterically hindered endotransition state. The antitumor activity of some of spiro-tryptanthrin derivatives against erythroleukemia (K562), cervical carcinoma (HeLa) and colon carcinoma (CT26) cell lines was evaluated in vitro by MTS-assay. [ABSTRACT FROM AUTHOR]

[Display omitted] The microwave-assisted cycloaddition of 2,6-disubstituted benzonitrile oxides to 1-iodobuta-1,3-diynes occurs at the iodo-substituted triple bond giving predominantly 5-alkynyl-4-iodo-1,2,3-isoxazoles. The Suzuki–Miyaura and Sonogashira cross-coupling reactions were used for the modification of the thus obtained 4-iodoisoxazoles. [ABSTRACT FROM AUTHOR]

Genetically encoded voltage indicators (GEVIs) have found wide applications as molecular tools for visualization of changes in cell membrane potential. Among others, several classes of archaerhodopsin-3-based GEVIs have been developed and have proved themselves promising in various molecular imaging studies. To expand the application range for this type of GEVIs, new variants with absorption band maxima shifted toward the first biological window and enhanced fluorescence signal are required. Here, we integrate computational and experimental strategies to reveal structural factors that distinguish far-red bright archaerhodopsin-3-based GEVIs, Archers, obtained by directed evolution in a previous study (McIsaac et al., PNAS, 2014) and the wild-type archaerhodopsin-3 with an extremely dim fluorescence signal, aiming to use the obtained information in subsequent rational design. We found that the fluorescence can be enhanced by stabilization of a certain conformation of the protein, which, in turn, can be achieved by tuning the p K value of two titratable residues. These findings were supported further by introducing mutations into wild-type archeorhodopsin-3 and detecting the enhancement of the fluorescence signal. Finally, we came up with a rational design and proposed previously unknown Archers variants with red-shifted absorption bands (λ a value of two titratable residues. These findings were supported further by introducing mutations into wild-type archeorhodopsin-3 and detecting the enhancement of the fluorescence signal. Finally, we came up with a rational design and proposed previously unknown Archers variants with red-shifted absorption bands (λ max up to 640 nm) and potential-dependent bright fluorescence (quantum yield up to 0.97%)., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)