Improved AMBER torsional parameters for the N-N rotational barrier in diacylhydrazines.

ABSTRACT

The structure and rotational barrier for substituted diacylhydrazines are of significant interest given the role this functionality plays in peptidomimetics and ecdysone agonists, the latter of which have application as extremely selective insecticides. Ab initio calculations show that the lowest energy conformations are typically nonplanar with essentially perpendicular nitrogen lone pairs. Molecular mechanics calculations using the AMBER force field in MacroModel yield minima and rotational barriers that are both quantitatively and qualitatively inconsistent with the ab initio results. In this work the AMBER N-N rotational barriers for all configurations of the parent, methyl and di-methyl substituted diformylhydrazines have been fitted to MP2/6-31 + G relative energies. The resulting AMBER torsional parameters have been validated by calculating the rotational barriers for N-t-butyl substituted diformylhydrazine, dibenzoylhydrazine and an azadipeptide. In each case the new AMBER rotational barriers compare favorably with the corresponding MP2 calculated rotational barriers.