PM6 and PDDG vs. DFT: A Computational Assessment of the Stability of cis and trans para Amino-dichloro Chalcone Isomers.

Chalcone molecules are well known for their versatile chemical properties and diverse applications in pharmaceuticals and materials science, making their conformational stability vital for understanding their behavior. However, because DFT calculations are computationally expensive, this study aims to evaluate whether semi-empirical methods such as PM6 and PDDG can serve as qualitatively reliable alternatives for assessing the configurational and geometrical stability of chalcone isomers. This study investigates model compounds (E) or (Z)-1-(4-aminophenyl)-3-(i,j-dichlorophenyl) prop-2-en-1-one, abbreviated as trans and cis chalcone. Dihedral scan results showed that PDDG predicts trans chalcones to prefer the s-cis conformation, consistent with DFT/B3LYP (6-311G (d,p)) calculations. Regarding syn and anti-syn Cl substitution patterns relative to the carbonyl direction and conformation, PDDG prefers the syn conformer in all trans chalcones, findings that agree with DFT, except for the (i=3, j=4) isomer. PM6 also agreed with DFT in predicting the anti-syn conformation for both trans and cis (3,4) isomers. For cis isomers, there is general agreement among PM6, PDDG, and DFT that they predominantly favor the anti-syn conformation over the syn. However, exceptions include the (3,4) isomer in DFT and PDDG, which prefer the syn conformation. PDDG agrees with DFT that all trans isomers are consistently more stable than cis isomers. These findings demonstrate that semi-empirical methods, particularly PDDG, can offer a cost-effective and reasonably accurate alternative for preliminary conformational stability assessments of chalcone derivatives. PDDG emerges as a more consistent and computationally efficient qualitative alternative to DFT, whereas PM6 shows less reliable agreement and should be applied with caution.