TY - JOUR

T1 - Photocaging of Carboxylic Function Bearing Biomolecules by New Thiazole Derived Fluorophore

AU - Gagarin, Aleksey A

AU - Minin, Artem S

AU - Shevyrin, Vadim A

AU - Kostova, Irena P

AU - Benassi, Enrico

AU - Belskaya, Nataliya P

N1 - Acknowledgements: We thank Russian Science Foundation (project 20-13-00089) for financially supporting. The administrative support received by the Europian Union-Next Generation EU, through the National Recovery and Resilience Plan of the republic of Bulgaria, project No. BG-PRP-2.004-0004-C01-is acknowledged. This work was performed using the equipment of the Shared Research Centre of Scientific Equipment SRC IIP UrB RAS. We also gratefully acknowledge the Siberian Branch of the Russian Academy of Sciences (SB RAS) Siberian Supercomputer Centre for providing supercomputer facilities. All authors have read and agreed to the published version of the manuscript. © 2023 Wiley-VCH GmbH.

PY - 2023/10/23

Y1 - 2023/10/23

N2 - The design and synthesis of a new fluorophore containing an arylidene thiazole scaffold resulted in a compound with good photophysical characteristics. Furthermore, the thiazole C5-methyl group was easily modified into specific functional groups (CH2 Br and CH2 OH) for the formation of a series of photocourier molecules containing model compounds (benzoic acids), as well as prodrugs, including salicylic acid, caffeic acid, and chlorambucil via a "benzyl" linker. Spectral characteristics (1 H, 13 C NMR, and high-resolution mass spectra) corresponded to the proposed structures. The photocourier molecules demonstrated absorption with high values of coefficient of molar extinction, exhibited contrasting green emission, and showed good dark stability. The mechanism of the photorelease was investigated through spectral analysis, HPLC-HRMS, and supported by TD-DFT calculations. The photoheterolysis and elimination of carboxylic acids were proved to occur in the excited state, yielding a carbocation as an intermediate moiety. The fluorophore structure provided stability to the carbocation through the delocalization of the positive charge via resonance structures. Viability assessment of Vero cells using the MTT-test confirmed the weak cytotoxicity of prodrugs without irradiation and it increase upon UV-light.

AB - The design and synthesis of a new fluorophore containing an arylidene thiazole scaffold resulted in a compound with good photophysical characteristics. Furthermore, the thiazole C5-methyl group was easily modified into specific functional groups (CH2 Br and CH2 OH) for the formation of a series of photocourier molecules containing model compounds (benzoic acids), as well as prodrugs, including salicylic acid, caffeic acid, and chlorambucil via a "benzyl" linker. Spectral characteristics (1 H, 13 C NMR, and high-resolution mass spectra) corresponded to the proposed structures. The photocourier molecules demonstrated absorption with high values of coefficient of molar extinction, exhibited contrasting green emission, and showed good dark stability. The mechanism of the photorelease was investigated through spectral analysis, HPLC-HRMS, and supported by TD-DFT calculations. The photoheterolysis and elimination of carboxylic acids were proved to occur in the excited state, yielding a carbocation as an intermediate moiety. The fluorophore structure provided stability to the carbocation through the delocalization of the positive charge via resonance structures. Viability assessment of Vero cells using the MTT-test confirmed the weak cytotoxicity of prodrugs without irradiation and it increase upon UV-light.

KW - TD-DFT calculations

KW - fluorescence

KW - photodissociation

KW - photoreleasing protecting groups

KW - thiazole

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85171308342&origin=inward&txGid=67993c268d508c19d7b9c24f525bf2a7

UR - https://www.mendeley.com/catalogue/2c1e5aca-fcf6-38b5-8e86-64032746efe7/

U2 - 10.1002/chem.202302079

DO - 10.1002/chem.202302079

M3 - Article

C2 - 37530503

VL - 29

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

SN - 0947-6539

IS - 59

M1 - e202302079

ER -