Photophysical behavior of a potential drug candidate, trans-[2-(4-methoxystyryl)]quinoline-1-oxide tuned by environment effects

- The molecule crystallizes in orthorhombic unit cell, space group Pbca.
- The pKa* value is about thousand fold greater than in the ground state.
- Variation of emission colors occurs in different media.
- In acidified water, the CT nature of S1 state increases.
- Excited state dynamics is viscosity independent.

Styryl and/or quinoline structural fragments, present in a large number of bioactive substances, inspired the design of various new drug candidates. In this paper, we describe the photophysical behavior of trans-[2-(4-methoxystyryl)]quinoline-1-oxide (trans-MSQNO) on the basis of X-ray analysis data, theoretical calculations as well as steady state and time-resolved spectroscopy experiments in various media. The molecule crystallizes in orthorhombic unit cell containing eight molecules of N-oxide, space group Pbca. The NO bond is substantially shorter in comparison with the NO bond in the ZnTPP unit [1.3052(11) Å vs. 1.335(2) Å]. Variation of emission colors from the violet (~ 450 nm) through blue (480 nm), green (525 nm) and yellow (575 nm) is observed in different environments. Comparable values of lifetimes estimated both at ambient temperature and at 77 K suggest that excited state dynamics in this case is viscosity independent. DFT and TD DFT B3LYP/6-31G(d, p) calculations performed for four different trans-MSQNO rotamers in the gas phase, as well as nonpolar and polar media (PCM model) suggest that an equilibrium between them can be significantly altered even by a relatively weak interactions with the environment. It is suggested that varying intensity ratios of experimental absorption bands in different media may be due to the dominant share of one or more rotamers of the excited trans-MSQNO molecule. Gas phase calculations show also that the vertical ππ*, S0 → S1, transition resulting from the HOMO → LUMO electronic configuration exhibits only a partial CT nature. On the other hand, in polar media, a substantial increment of excited state dipole moment of all rotamers compared to the ground state, its increase with increasing solvent polarity and a significant red shift in the absorption and emission spectra, point to the enhanced CT nature of the S1 excited state. Hence, the trans-MSQNO molecule may be considered a subsequent styrylquinoline drug candidate where the CT drug-receptor interactions are of a high importance.

Graphical AbstractIn the gas phase, the molecule exists as the trans isomer in four rotameric forms (trans-syn MSQNO-00 and MSQNO-01 as well as trans-anti MSQNO-10 and MSQNO-11), depending whether the quinoline and the phenyl ring are placed on the same or on the opposite sides of the styryl bridge double bond. In the solid state only the trans, anti MSQNO-10 rotamer was detected.185