Conformational analysis of cellobiose by electronic structure theories q Alfred D. French a,⇑ , Glenn P. Johnson a , Christopher J. Cramer b , Gábor I. Csonka c a Southern Regional Research Center, U.S. Department of Agriculture, 1100 Robert E. Lee Blvd, New Orleans, LA 70124, USA b Department of Chemistry and Supercomputer Institute, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN 55455-0431, USA c Department of Chemistry, Budapest University of Technology and Economics, Budapest H-1111, Hungary article info Article history: Received 16 November 2011 Received in revised form 21 December 2011 Accepted 22 December 2011 Available online 3 January 2012 Keywords: Aqueous solvation Carbohydrate Cellulose Conformational analysis Disaccharide Mapping abstract Adiabatic //w maps for cellobiose were prepared with B3LYP density functional theory. A mixed basis set was used for minimization, followed with 6-31+G(d) single-point calculations, with and without SMD con- tinuum solvation. Different arrangements of the exocyclic groups (38 starting geometries) were considered for each //w point. The vacuum calculations agreed with earlier computational and experimental results on the preferred gas phase conformation (anti-/ H , syn-w H ), and the results from the solvated calculations were consistent with the (syn / H /w H conformations from condensed phases (crystals or solutions). Results from related studies were compared, and there is substantial dependence on the solvation model as well as arrangements of exocyclic groups. New stabilizing interactions were revealed by Atoms-In-Molecules theory. Published by Elsevier Ltd. 1. Introduction Computerized Ramachandran mapping studies of cellobiose were carried out more than 40 years ago. 1 Such studies, which cal- culate potential energy at increments of the torsion angles for the linkage bonds (/ and w), continue because of the important role of cellobiose as the shortest cellulose chain and because of continuing controversies about cellulose structure. In hopes of obtaining greater accuracy, several recent efforts have employed quantum mechanical (QM) electronic structure theory rather than the much faster empirical force field methods (molecular mechanics) used in most mapping studies. One important QM contribution confirms that the low-energy gas-phase structure has an anti-/ H , syn-w H conformation, with the O6 groups on the same side of the molecule. On the other hand, experimental solution 2 and crystal structures are, with one excep- tion, 3 in the syn / H /w H region wherein structures have the O6 groups on alternate sides. The anti-/ H , syn-w H conformation for the gas-phase was initially predicted by Strati et al., 4 and was sub- sequently confirmed by gas-phase experiments augmented by QM calculations. 5 Thus it appears that cellobiose undergoes a major conformational transformation (about 160° in /) when put into the vapor phase. More recently, adiabatic vacuum surfaces made with different empirical force fields were reported to be notably different 6 from Hartree Fock (HF) QM energy surfaces. 7 Although perfect agreement with the vacuum maps should not be expected because the empir- ical energy functions are often adjusted to work with specific mod- els of water molecules, the empirical surfaces also differed from each other. 6,8 Agreement is difficult to achieve because adiabatic //w maps for disaccharides are complex hypersurfaces that present energies based also on other variables, including orientations of ten exocyclic groups and pyranose ring puckering geometries. Reasonable comparisons among those methods were enabled by using the same set of starting geometries for each method. The starting geometries, with different arrangements of the exocyclic groups, can affect the energies nearly as much as variations of the linkage torsion angles. 7 The findings of significant discrepancies motivated further research with QM, seeking to learn whether high- er levels of QM theory would give results that are substantially different from the modest HF level. If not, and there is a convergence of QM results, then there should be confidence in empirical methods that can reproduce the QM results. Empirical methods are still nec- essary for studying the large-scale cellulose structures that contain tens of thousands of atoms. Another motivator for more QM work is that HF theory neglects important electron-correlation effects. New energy surfaces were expected to differ somewhat, but future calcu- lations would be more efficient if only starting geometries having low HF energies were tested. More computationally demanding lev- els of theory could be applied if time were not wasted on starting structures that possess high HF energy and are therefore unlikely to have low energy at higher levels of theory. 0008-6215/$ - see front matter Published by Elsevier Ltd. doi:10.1016/j.carres.2011.12.023 q Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture. ⇑ Corresponding author. Tel.: +1 504 286 4410; fax: +1 504 286 4419. E-mail address: Al.French@ars.usda.gov (A.D. French). Carbohydrate Research 350 (2012) 68–76 Contents lists available at SciVerse ScienceDirect Carbohydrate Research journal homepage: www.elsevier.com/locate/carres