Data from: Rapid assessment of conformational preferences in biaryl and aryl carbonyl fragments

The ability to rapidly assess the preferred conformation of key fragments
in a structure "by visual inspection" is a very useful starting
point in the process of drug design. With the ability to do so, one could
address questions like: "How could we avoid planarity in a
molecule?", "Will a molecule change its conformational
preference if we make it more or less basic?" or "How does this
electronic repulsion affect the conformational preference in the
system?" in timely fashion. In this paper, we describe how the
conformational energy profile (CEP, plot of energy as a function of
dihedral bond angle) of a fragment can be interpreted through the
understanding the interplay between resonance stabilization, steric
effects and electrostatic interactions. Fifty-nine biaryl and aryl
carbonyl fragments present in oral drugs or which are close derivatives
thereof were selected. Calculation of their CEPs using ab initio
methodology allowed us to conclude the relative importance of these
factors in the conformational preference of these fragments as follows:
steric repulsion > lone pair - lone pair repulsion > lone
pair - fluorine repulsion > resonance stabilization and, to
formulate "rules of thumb" that the practicing medicinal/organic
chemist can apply when analysing molecules that contain these fragments.