Get access

An ab initio molecular orbital study of intramolecular hydrogen bonding in ortho-substituted arylamides: Implications for the parameterization of molecular mechanics force fields

Authors

  • Zhiwei Liu,

    1. Department of Chemistry and Biochemistry and Center for Drug Design and Delivery, University of the Sciences in Philadelphia, 600 S. 43rd Street, Philadelphia, Pennsylvania 19104
    Search for more papers by this author
  • Alexey Teslja,

    1. Department of Chemistry and Pharmaceutial Science, Fairleigh Dickinson University, 285 Madison Avenue, Madison, New Jersey 07940
    Search for more papers by this author
  • Vojislava Pophristic

    Corresponding author
    1. Department of Chemistry and Biochemistry and Center for Drug Design and Delivery, University of the Sciences in Philadelphia, 600 S. 43rd Street, Philadelphia, Pennsylvania 19104
    • Department of Chemistry and Biochemistry and Center for Drug Design and Delivery, University of the Sciences in Philadelphia, 600 S. 43rd Street, Philadelphia, Pennsylvania 19104
    Search for more papers by this author

Abstract

The aromatic oligoamide (arylamide) foldamer class, characterized by the repetitive aromatic-amide pattern, is one of the most intensively studied foldamer families. In this article, the potential energy profiles with regard to torsional motions around the two types of aromatic-amide bonds (Ca[BOND]Cp and Ca[BOND]N) are obtained at the B3LYP/6-311G(d,p) level of theory. The effect of ortho substituents with different hydrogen bonding abilities (OCH3 vs. SCH3) on the torsional potential profiles is analyzed in detail. There are several findings that have implications in foldamer design. The ortho-SCH3 substituent on the benzene ring produces a much more flexible arylamide backbone with respect to the OCH3 substituent, as it restricts the Ca[BOND]Cp torsion to a lesser extent. Interestingly, the rigidifying effect of the ortho-SCH3 substituent on the Ca[BOND]N torsion is very similar to that of the OCH3 substituent on the same linkage type. In addition, the SCH3 substituent prefers a perpendicular orientation with respect to the benzene ring to the in-plane one. It is also found that reparameterization of the corresponding torsional parameters, sometimes specific to the ortho substituent type, in the general amber force field is necessary for an accurate description of the backbone torsions in arylamides. Six sets of partial charge/torsional parameters for each linkage (Ca[BOND]Cp or Ca[BOND]N)/substituent (OCH3 or SCH3) combination are obtained based on the ab initio torsional profiles. Initial assessments of these parameters show good agreement with the ab initio results. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011

Get access to the full text of this article

Ancillary