The Dipole Climbs, S₁ Barely Budges: Solvent-Resolved DFT and TD-DFT of an Alanine-Derived 4-Hydroxypyrrole

Introduction

Pyrrole rings are common motifs in medicinal chemistry. This study examines the alanine-derived 4-hydroxypyrrole 1-(4-hydroxy-2,5-dimethyl-1H-pyrrol-3-yl)ethan-1-one in the gas phase, chloroform, and methanol. The calculations were designed to determine whether the medium affects mainly the dipole moment, excitation energies, or oscillator-strength distribution.

Methods

A conformer recovered from GOAT/GFN2-xTB exploration was optimized at PBE0-D4/def2-TZVP with ORCA 6.1 in the gas phase and using SMD for chloroform and methanol. Harmonic frequencies verified the optimized structures as local minima. Thirty singlet excited states were calculated with TD-DFT/PBE0.

Results

No imaginary frequencies were found for any optimized structure. The dipole moment increased from 5.658 D in the gas phase to 7.715 D in chloroform and 8.961 D in methanol. The Kohn–Sham HOMO–LUMO gap varied only from 4.740 to 4.769 eV. S₁ appeared at 323.8, 324.3, and 325.2 nm, with oscillator strengths of 0.0414, 0.0563, and 0.0545, respectively. The brightest calculated transition occurred at 205.7 nm in the gas phase, 203.6 nm in chloroform, and 200.3 nm in methanol. Its oscillator strength increased from 0.285 to 0.445 and 0.452 in solution. The brightest transition corresponded to S₆ in the gas phase and S₅ in both solvents.

Conclusions

Within the continuum-solvation treatment, increasing solvent polarity mainly affected the calculated ground-state dipole moment and the oscillator strengths of higher-energy transitions. By comparison, S₁ and the Kohn–Sham HOMO–LUMO gap changed very little across the three environments. The solvent response was therefore expressed more clearly in molecular polarization and calculated transition intensity than in the lowest excitation energy.