Photocaging of Carboxylic Function Bearing Biomolecules by New Thiazole Derived Fluorophore

• Published in: Chemistry : a European journal Vol. 29; no. 59; p. e202302079
• Main Authors: Gagarin, Aleksey A., Minin, Artem S., Shevyrin, Vadim A., Kostova, Irena P., Benassi, Enrico, Belskaya, Nataliya P.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 23.10.2023; Wiley Subscription Services, Inc
• Subjects: Benzoic acid; Biomolecules; Caffeic acid; Carboxylic acids; Chemical compounds; Chemistry; Chemistry, Multidisciplinary; Chlorambucil; Cytotoxicity; Drugs; Functional groups; Irradiation; Liquid chromatography; Mass spectra; NMR; Nuclear magnetic resonance; Physical Sciences; Prodrugs; Salicylic acid; Science & Technology; Spectral analysis; Spectrum analysis; Stability analysis; Structural stability; Toxicity testing; Vero cells; ORGANIC-PHOTOCHEMISTRY; BODIPY; DESIGN; MECHANISMS; photoreleasing protecting groups; RELEASE; TD-DFT calculations; photodissociation; DENSITY; fluorescence; thiazole; CHEMISTRY; PHOTOREMOVABLE PROTECTING GROUPS; PHOTODECARBOXYLATION; Fluorescence, Photodissociation, Photoreleasing protecting groups (PPG), TD-DFT calculations, Thiazole
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202302079

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 (CH2Br and CH2OH) 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 (1H, 13C 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. We report on synthesis of a new bright blue-green fluorophore for targeted delivery of biologically active substances containing a carboxyl group. The resulting hybrids were thoroughly studied to understand their photophysical properties and behavior under various conditions. The mechanism of photorelease of caging molecules were studied. Biological experiments demonstrated their bioavailability and easy penetration into living cells.image