Vibrational Spectroscopic and Quantum-Chemical Study of Indole–Ketone Hydrogen-Bonded Complexes

TL;DR

This study combines spectroscopy and quantum chemistry to analyze hydrogen bonds between indole and various ketones, revealing how structural and electronic factors influence binding strength.

Contribution

The study introduces a multivariate regression model linking experimental binding constants to quantum-chemical descriptors for hydrogen-bonded complexes.

Findings

Cyclohexanone forms the strongest hydrogen-bonded complex with indole, while benzophenone forms the weakest.

Quantum-chemical calculations confirmed hydrogen bonds and additional weak interactions that stabilize the complexes.

Strong correlations (R² = 0.928 and 0.957) were found between experimental binding constants and theoretical descriptors like binding energy and electrophilicity index.

Abstract

This study investigates the structural and energetic properties of hydrogen-bonded complexes between indole and a range of aliphatic, cyclic, and aromatic ketones using a combined vibrational spectroscopic and quantum-chemical approach. FTIR measurements in CCl4 revealed redshifts in the N-H stretching vibration of indole upon complexation, with formation constants (Ka) ranging from 0.3 to 6.6 M−1. Cyclohexanone displayed the strongest binding, while benzophenone exhibited the weakest interaction. Quantum-chemical calculations, employing CREST and MMFF94 conformational sampling, along with M06-2X/6-311++G(d,p) optimizations, confirmed the formation of hydrogen bonds and additional weak interactions that govern the stability of the complex. QTAIM analysis revealed moderate closed-shell hydrogen bonds with electron densities at the bond critical points (ρ) ranging from 0.010 to 0.019 a.u. and potential energy densities (V) from −18.4 to −36.4 kJ mol−1. Multivariate regression analysis established strong correlations (R2 = 0.928 and 0.957) between experimental binding constants and theoretical descriptors, including binding energy, NBO charge on oxygen atom, ionization potential, and electrophilicity index, highlighting the interplay between geometric, electronic, and global reactivity factors. This comprehensive study underlines the predictive power of spectroscopic and quantum descriptors for assessing hydrogen bonding in biologically relevant systems.

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