Tuning sulfur-induced red shift of coelenteramide fluorescence: linking experiment and theory

Sulfur-substituted coelenteramide derivatives were synthesized and characterized to investigate the influence of chemical modifications on their photophysical behavior. Fluorescence spectra recorded in methanol revealed a consistent bathochromic shift compared to the reference compound h-coelenteramide 3. Time-dependent density functional theory (TD-DFT), combined with Natural Bond Orbital (NBO) and Natural Transition Orbital (NTO) analyses, was employed to model the electronic structure and excitation properties of the compounds 3 and 4a-f. The calculations reproduced the experimental shifts with good consistency and highlighted the key role of sulfur lone pairs in modulating the electronic structure and indirectly stabilizing the excited state, rather than directly enhancing the intramolecular charge-transfer (ICT) process. Theoretical results revealed that the sulfur lone pairs interact with both pi* and sigma* orbitals, one promoting delocalization and the other contributing through hyper-conjugation, thereby modulating the ground-state electronic structure and favoring stabilization of the excited state. NTO analysis further confirmed that sulfur is not directly involved in the S0 -> S1 transition, but indirectly influences the emission properties. The comparison between compound 3 and the sulfur-substituted derivatives focuses on how small electronic modifications influence fluorescence, with implications for the design of new chemiluminescent and bioluminescent intermediates.