Experimental, Hartree-Fock, and Density Functional Theory Investigations of the Charge Density, Dipole Moment, Electrostatic Potential, and Electric Field Gradients in L-Asparagine Monohydrate William D. Arnold, † Lori K. Sanders, † Michael T. McMahon, † Anatoliy V. Volkov, ‡ Guang Wu, ‡ Philip Coppens, ‡ Scott R. Wilson, † Nathalie Godbout, † and Eric Oldfield* ,† Contribution from the Department of Chemistry, UniVersity of Illinois at Urbana-Champaign, 600 South Mathews AVenue, Urbana, Illinois 61801, and Chemistry Department, State UniVersity of New York at Buffalo, Buffalo, New York 14260-3000 ReceiVed February 1, 2000 Abstract: We have investigated the charge density, F(r), its curvature, ∂ 2 F/∂r ij , the dipole moment, µ, and the electrostatic potential, Φ(r), in L-asparagine monohydrate by using high-resolution single-crystal X-ray crystallography and quantum chemistry. In addition, we have compared electric field gradient, ∇E, results obtained from crystallography and quantum chemistry with those obtained from single-crystal 14 N nuclear magnetic resonance spectroscopy. A multipole model of the X-ray F(r) is compared to Hartree-Fock and density functional theory predictions, using two different large basis sets. The quality of the calculated charge densities is evaluated from a simultaneous comparison of eight Hessian-of-F(r) tensors at bond critical points between non-hydrogen atoms. These tensors are expressed in an icosahedral representation, which includes information on both tensor magnitude and orientation. The best theory-versus-experiment correlation is found at the B3LYP/6-311++G(2d,2p) level, which yields a slope of 1.09 and an R 2 value of 0.96. Both DFT and HF results give molecular dipole moments in good accord with the value extracted from the X-ray diffraction data, 14.3(3) D, and both sets of calculations are found to correctly reproduce the experimental molecular electrostatic potential, Φ(r). The intermolecular hydrogen bond F(r) is also subjected to a detailed theoretical and experimental topological analysis, and again good agreement is found between theory and experiment. For the comparison of the ∇E tensors, the icosahedral representation is again used. There is found to be moderate accord between theory and experiment when using results obtained from diffraction data, but much better accord when using results obtained from NMR data (slope ) 1.14, R 2 ) 0.94, for the 12 icosahedral tensor elements for N1 and N2). Overall, these results strongly support the idea that both HF and DFT methods give excellent representations of the electrostatic properties F(r), ∂ 2 F/∂r ij , µ, Φ(r), and ∇E, for crystalline L-asparagine monohydrate, encouraging their future use in situations where experimental results are lacking, such as in peptides and in enzyme active sites. Introduction There is currently considerable interest in using quantum chemical methods to investigate structure and bonding in molecules of ever increasing size and to help predict and refine the structures of molecules using spectroscopic observables. 1 In our group at the University of Illinois, we have been using quantum chemical methods to help interpret both isotropic chemical shifts and chemical shift tensors in proteins and model systems, to provide new approaches to protein structure refinement. 1-4 In the case of 13 C R , 13 C  , and 13 C γ shift determinations, we have generally used Hartree-Fock (HF) methods, 5,6 while in the case of metalloporphyrins, we have used density functional theory (DFT) methods with hybrid functionals to investigate both metal and ligand shieldings, 7-10 since these give the best agreement between theory and experiment. And, as a bonus from the SCF part of these calculations, we have access to a large base of electrostatic properties which can be derived at little extra computational cost. The general question then arises: How accurate might these computed electrostatic properties, such as the charge density, F(r), its curvature, ∂ 2 F/ ∂r ij , the dipole moment, µ, the electrostatic potential, Φ(r), and the electric field gradient, ∇E, be? We report here high-resolution single-crystal X-ray diffraction data (obtained by using synchrotron radiation with an area detector) on L-asparagine‚H 2 O, which contains a hydrogen- bonded amide group, and we investigate the F(r), ∂ 2 F/∂r ij , µ, Φ(r), and ∇E values determined both experimentally (from † University of Illinois. ‡ State University of New York. (1) Oldfield, E. J. Biomol. NMR 1995, 5, 217-225. (2) deDios, A. C.; Pearson, J. G.; Oldfield, E. Science 1993, 260, 1491- 1496. (3) Pearson, J. G.; Wang, J.; Markley, J. L.; Le, H.; Oldfield, E. J. Am. Chem. Soc. 1995, 117, 8823-8829. (4) McMahon, M. T.; deDios, A. C.; Godbout, N.; Salzmann, R.; Laws, D. D.; Le, H.; Havlin, R. H.; Oldfield, E. J. Am. Chem. Soc. 1998, 120, 4784-4797. (5) Havlin, R. H.; Le, H.; Laws, D. D.; deDios, A. C.; Oldfield, E. J. Am. Chem. Soc. 1997, 119, 11951-19958. (6) Pearson, J. G.; Le, H.; Sanders, L. K.; Godbout, N.; Havlin, R. H.; Oldfield, E. J. Am. Chem. Soc. 1997, 119, 11941-11950. (7) Salzmann, R.; Kaupp, M.; McMahon, M.; Oldfield, E. J. Am. Chem. Soc. 1998, 120, 4771-4783. (8) Godbout, N.; Oldfield, E. J. Am. Chem. Soc. 1997, 119, 8065-8069. (9) Havlin, R. H.; McMahon, M.; Srinivasan, R.; Le, H.; Oldfield, E. J. Phys. Chem. 1997, 101, 8908-8913. (10) Godbout, N.; Havlin, R.; Salzmann, R.; Wojdelski, M.; Debrunner, P. G.; Oldfield, E. J. Phys. Chem. 1998, 102, 2342-2350. 4708 J. Am. Chem. Soc. 2000, 122, 4708-4717 10.1021/ja000386d CCC: $19.00 © 2000 American Chemical Society Published on Web 04/27/2000