Excited‐State Proton Transfer Can Tune the Color of Protein Fluorescent Markers

Abstract

We show by quantum mechanical/molecular mechanical (QM/MM) simulations that phenylbenzothiazoles undergoing an excited-state proton transfer (ESPT) can be used to probe protein binding sites. For 2-(2′-hydroxy-4′-aminophenyl)benzothiazole (HABT) bound to a tyrosine kinase, the absolute and relative intensities of the fluorescence bands arising from the enol and keto forms are found to be strongly dependent on the active-site conformation. The emission properties are tuned by hydrogen-bonding interactions of HABT with the neighboring amino acid T766 and with active-site water. The use of ESPT tuners opens the possibility of creating two-color fluorescent markers for protein binding sites, with potential applications in the detection of mutations in cancer cell lines

Mechanistic insights into excited state intramolecular proton transfer in isolated and metal chelated supramolecular chemosensors

“…1), which is known to undergo ESIPT upon electronic excitation. 27 Transient absorption measurements following 340 nm excitation of HBO in cyclohexane solution show enol → keto tautomerism occurring as a result of ESIPT on a timescale of ∼100 fs or less [28][29][30][31] consistent with the results of mixed quantum/classical molecular dynamics calculations by Daengngern et al 32 The thio-analogue of HBO has also been studied recently by Barbatti and co-workers 33 who proposed, on the basis of the deduced ultrafast excited state intra-and inter-molecular PT, that this molecule could be a good candidate for use as a protein fluorescent marker.…”

“…Following photoinduced tautomerism, we consider two possible fates for a keto tautomer in its S 1 state: fluorescence and internal conversion. Analogy with molecules like 2-(2′-hydroxyphenyl)benzotriazole 23 and 2-(2′-hydroxyphenyl)benzothiazole 33 suggests that E → Z isomerism around the C(3)vC (9) bond (in the case of HBO, (C(6)vC (17) in the case of HDBO)) might offer a route from the keto minimum to a minimum energy (ME)CI between the S 1 and S 0 PESs. Fig.…”

Detection of Chemical Weapon Agents Using Spectroscopic Probes: A Computational Study

“…It is well known that spectroscopic properties are modulated by structural features [42][43][44][45][46]. us, to take into account the geometric effects on the nerve agents, we have used chemometric techniques, such as surface response methodology [47].…”

6-Benzothiazolyl Ureas, Thioureas and Guanidines are Potent Inhibitors of ABAD/17β-HSD10 and Potential Drugs for Alzheimer"s Disease Treatment: Design, Synthesis and in vitro Evaluation

“…117 [21]. Based on this method, the ElogD was determined accordingly [22]. All chemicals were purchased from Sigma-Aldrich (St. Louis, MO, USA The capacity factors (Eq.…”