ABSTRACT
Hydroxyphenyl-azoles are among the most popular ESIPT (Excited State Intramolecular Proton Transfer) scaffolds and as such, they have been thoroughly studied. Nevertheless, some aspects regarding the interplay between the emissive properties of these fluorophores and the size of their π-conjugated framework remain controversial. Previous studies have demonstrated that benzannulation of 2'-hydroxyphenyl-oxazole at the phenol group of the molecule can lead to either red- or blue-shifted fluorescence emission, depending on the site where it occurs. In this report, benzannulation at the heterocyclic unit (the oxazole site) is analysed in order to get the whole picture. The extension of π-conjugation does not significantly affect the ESIPT emission wavelength, but it leads instead to higher energy barriers for proton transfer in the first excited singlet state, as a consequence of dramatic changes in the charge transfer character of excitation caused by successive benzannulation. Theoretical calculations revealed an interesting connection between intramolecular charge transfer and excited-state aromaticity in the S1 state. The theoretical approach presented herein allows the behaviour of hydroxyphenyl-oxazoles in the excited state to be rationalized and, more generally, a deeper understanding of the factors governing the ESIPT process to be obtained, a crucial point in the design of new and efficient fluorophores.
ABSTRACT
ESIPT (Excited State Intramolecular Proton Transfer) to C atom in 2-phenylphenol is known to be an intrinsically inefficient process. However, to the best of our knowledge, a structure-ESIPT efficiency relationship has not been elucidated yet. Here, we show that there exists a competitive interplay between photoacidity and ESIPT efficiency for the 2-phenylphenol system. The attachment of electron withdrawing groups to the phenol moiety promotes adiabatic deprotonation in the excited state and diminishes the charge transfer character of the excitations, and both these factors contribute in decreasing the ESIPT reaction yield. On the other hand, unfavorable conformational distribution in the ground state also appears as another important aspect responsible for the low ESIPT extent of 2-phenylphenol. A new derivative bearing electron donating, bulky substituents at ortho and para positions of the phenol ring shows an outstanding ESIPT performance, which demonstrates that the efficiency of the process can be significantly enhanced by modifying the substitution pattern. We anticipate that our results will help to guide the molecular designing of new compounds with high ESIPT efficiency.
ABSTRACT
The zinc enzymes metallo beta-lactamases counteract the beneficial action of beta-lactam antibiotics against bacterial infections, by hydrolyzing their beta-lactam rings. To understand structure/function relationships on a representative member of this class, the B2 M beta L CphA, we have investigated the H-bond pattern at the Zn enzymatic active site and substrate binding mode by molecular simulation methods. Extensive QM calculations at the DFT-BLYP level on eleven models of the protein active site, along with MD simulations of the protein in aqueous solution, allow us to propose two plausible protonation states for the unbound enzyme, which are probably in equilibrium. Docking procedures along with MD simulations and QM calculations suggest that in the complex between the enzyme and its substrate (biapenem), the latter is stable in only one of the two protonation states, in addition it exhibits two different binding modes, of which only one agrees with previous proposals. In both cases, the substrate is polarized as in aqueous solution. We conclude that addressing mechanistic issues on this class of enzymes requires a careful procedure to assign protonation states and substrate docking modes.
