Effect of Molecular Structure on the B3LYP-Computed HOMO–LUMO Gap: A Structure −Property Relationship Using Atomic Signatures

Compounds possessing
a small highest occupied molecular orbital–lowest
unoccupied molecular orbital (HOMO–LUMO) gap (Egap) are highly desirable due to their instability and
reactivity, making them useful for a wide range of applications. However,
the search for new organic compounds with a low Egap is an expensive endeavor due to the exponentially
increasing pool of virtual compounds. Accordingly, in this study,
atomic Signatures were utilized as molecular descriptors to investigate
the correlation between the molecular structure and the B3LYP-computed Egap, thus aiding in the development of a quantitative
structure–property relationship (QSPR). An easy-to-use robust
model was constructed using forward-stepping multilinear regression
with leave-one-out cross validation, resulting in a regression coefficient
(r2) of 0.86 and a predictability (q2) of 0.76. The use of atomic Signatures as
molecular descriptors successfully inferred correlations between different
structural motifs and Egap. The atomic
fragments containing π-bonds in various aromatic compounds were
found to be the most significant atomic Signatures, explaining nearly
50% of the variance in the data, with regression coefficients that
decreased Egap. This is attributed to
π-electron delocalization, making this molecular fragment a
reactive site in a molecule. Finally, an external test set was used
to further evaluate the model’s predictive performance. The
developed QSPR can be utilized as a reliable initial screening tool
to identify potential candidates possessing low Egap values.