Vitamin C at 120 K: Experimental and theoretical study of the charge density

Vitamin C is an extremely interesting molecule, not only for its important biological properties, but also for its crystal structure in which the formation of several hydrogen bonds plays an important role. We have collected X-ray diffraction data at - 153°C up to sinθ/λ = 1.17 A°^-1. The crystals do not undergo any phase transformation and the space group remains P2₁ with two independent molecules in the asymmetric unit. In the final difference Fourier map non-spherical electron density in the bonding regions was clearly indicated. A study by means of a multipole expansion of the electron density has been performed and the experimental electrostatic potential maps obtained. We have also computed the electron density by means of the crystalorbital approach as coded in the program CRYSTAL95 [R. Dovesi et al., CRYSTAL95 User's Manual, University of Torino]. A complete ab initio conformational analysis of the isolated molecule has also been carried out at HF-SCF and density functional level, with reasonably large basis sets. The results of this analysis are: (i) vitamin C molecules are tightly bound in the crystal by a network of eight intermolecular H-bonds per molecule. The relative strength of these bonds is well accounted for by the experimental electrostatic potential. No relevant intramolecular interactions are present; (ii) CRYSTAL95 calculations give a value of 44 kcal mol^-1 as the sublimation energy per mole of molecules, computed at correlated level with 6-21G(d,p) and Perdew 91 potential [J.P. Perdew and Y. Wang, Phys. Rev. B, 45 (1992) 13244; M. Causà and A. Zupan, Chem. Phys. Lett., 220 (1994) 145]; (iii) the CRYSTAL95 electron density maps are in good agreement with the experimental ones; (iv) the calculations on the isolated molecule reveal that the most stable conformers are different from the X-ray structure and are characterized by intramolecular H-bonds; the maximum energy difference among the 11 conformers taken into account is less than 6 kcal mol^-1; (v) the NMR analysis in water reveals that the least populated side-chain conformation around bond C5-C6 is that found in our computed gas-phase conformers with the most folded-up side chain, which are indeed less prone to be solvated.