A Novel Interpretation Of The Rotation Barrier In Biphenyl: Are Textbooks Misleading?

Biphenyl is of significant interest as a molecular core for many current compounds currently under proposal for clinical trials[1]. This is due to its ability to stereo-control the formation of the drug according to substituent groups and their position in the phenyl ring. As a core it features in 2.6 % of all CSD structures and 0.2 % of all PDB structures. In the CSD it is the most frequently observed core, and is the 7th most frequent in the PDB.The cause of these rotation barriers seen in the molecule is still controversial and the literature is in need of a minimal and rigorous method to give clear answers built on quantitative results [2]. Here we aim to offer a novel interpretation of the cause of the rotation barriers, based on a rigorous analysis of the energetics of biphenyl at the atomic level. We aim to show that it is possible to combine qualitative insight with a modern and minimal source of physical quantities.Within the context of Quantum Chemical Topology (QCT), the Interacting Quantum Atoms (IQA)[3],[4],[5] approach provides the quantitative framework of our analysis. We focus on two key IQA energies which sum to recover the molecular energy: the atomic self-energy (ESelfA) and the interatomic interaction energy (EInterA,A’)[3]. The latter used in the IQA formalism will allow an inter-atomic interaction insight through both exchange and classical electrostatic energies