Structures of some substituted nitrophenols determined by ab initio computation: On the origin of heterocliticity in anti-nitrophenol antibodies

Christian S. Parry, Bernard R. Brooks, Nikita Matsunaga, L. Mario Amzel

Research output: Contribution to journalArticlepeer-review


Nitrophenol and its derivatives are widely used in analytical chemistry and also as haptens in immunology. In C57BL/6 mice the iodo derivative binds the antibody to nitrophenol over ten times more efficiently than the eliciting hapten nitrophenol. The latter result is unusual since it is expected that the eliciting hapten should bind its antibody best and all other haptens bind less well. Our X-ray crystallographic and molecular modelling studies showed that in the structures of the antibody in complex with nitrophenol and iodonitrophenol the haptens bind in a cavity making van der Waals and hydrogen bonding contacts with the antibody. The iodine in the iodonitrophenol-antibody complex points away from the binding site and does not provide additional contacts with the protein. In order to understand how the iodine substitution in the nitrophenyl ring contributes to the binding of the hapten to the antibody we have carried out ab initio molecular orbital studies on nitrophenol, iodonitrophenol and their corresponding anions. We have approached this problem by analyzing the electron distribution, bond and molecular energies. The wavefunction was determined at the Hartree-Fock level using the basis set 3-21G(d,p). Optimized equilibrium geometries were characterized by harmonic vibrational analysis. Atomic charges were obtained from Mulliken's population analysis and by the direct integration of molecular electron densities using Bader's "Atoms In Molecules". We find that the substitution with iodine changes the charge distribution in the nitrophenyl ring, thus enhancing the electrostatic interaction of the ring with the antibody heavy chain Lysine 59 and Arginine 50. This explains how the iodine increases the binding affinity without directly interacting with the protein.

Original languageEnglish (US)
Pages (from-to)555-563
Number of pages9
JournalJournal of Molecular Structure: THEOCHEM
StatePublished - Jun 30 1997


  • Anti-nitrophenol antibodies
  • Heterocliticity
  • Nitrophenol

ASJC Scopus subject areas

  • Biochemistry
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry


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