A Molecular Modeling Case Study on the Thermodynamic Partition of DIPNs Derived from Naphthalene and C₃-Sources Using...

Recently, an article was published in which a more accurate pre-screening method compared to MMFF for conformer distributions in flexible organic molecules was presented. However, experimental data on conformer distributions are almost completely lacking. Therefore, old experimental and computational work on the thermodynamic partition of DIPN isomers was revisited to compare the new method, corrected MMFF (cMMFF), with MMFF as a pre-screening tool. Next, the preliminary conformer distributions were used as input for higher-level QM calculations to yield more reliable conformer distributions. Generally, it was found that cMMFF yields smaller energy differences between DIPN isomers and conformers of a DIPN isomer than MMFF, in line with the results of DFT methods B3LYP and B3PW91, used in higher-level calculations. MP2 turned out to be a remarkable outlier, yielding even smaller energy differences both between DIPN isomers and conformers of a DIPN isomer. Preliminary conformer distributions of DIPN isomers obtained with MMFF and optimized with B3LYP and B3PW91 yielded excellent thermodynamic equilibrium partitions of DIPN isomers compared to the available experimental data. Preliminary conformer distributions of DIPN isomers obtained with cMMFF and optimized with B3LYP and B3PW91 performed less well. However, this seems due to a small effect on the energy (~4 kJ/mol) of the local geometry of the β-isopropyl group on naphthalene, which still strongly affects the thermodynamic equilibrium partitions. To obtain a more balanced judgement on the newly proposed method and the existing ones, more comparisons between experimental and computational data on small molecules with a higher degree of flexibility are needed.