The focus of our research is to bridge solid state structural studies with computational (ab initio) modelling methods by exploring the influence of different functional groups and their position in semi-rigid small drug-like molecules.1-3 A 3×3 isomer grid of nine N-(tolyl)pyridinecarboxamides (C13H12N2O) as NxxM (x = para-/meta-/ortho-) (Scheme 1A) has been synthesised and characterised to evaluate and correlate structural relationships from both solid-state (Table 1, Figs. 1,2,4) and ab initio calculations (Fig. 3). The effect of pyridinoyl group (Nx) and methyl group (xM) substitution patterns on molecular structure and conformations (syn/anti, Scheme 1B) from calculations (gas phase and solvated forms), as well as on crystal packing and conformations in solid state is explored, allowing evaluation and rationalisation of disorder and unexpected conformations in the solid state structures.