Governing Parameters of Long-Range Intramolecular S-to-N Acyl Transfers within (S)-Acyl Isopeptides

Jean-Christophe M Monbaliu; Georges Dive; Christian V Stevens; Alan R Katritzky

doi:10.1021/ct300830k

Governing Parameters of Long-Range Intramolecular S-to-N Acyl Transfers within (S)-Acyl Isopeptides

J Chem Theory Comput. 2013 Feb 12;9(2):927-34. doi: 10.1021/ct300830k. Epub 2013 Jan 4.

Authors

Jean-Christophe M Monbaliu^{1

2}, Georges Dive³, Christian V Stevens², Alan R Katritzky^{1

4}

Affiliations

¹ Center for Heterocyclic Compounds, Department of Chemistry, University of Florida , Gainesville, Florida 32611-7200, United States.
² Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University , B-9000 Ghent, Belgium.
³ Center of Protein Engineering, Institut de Chimie, University of Liège , Bâtiment B.6, B-4000 Sart Tilman, Liège, Belgium.
⁴ Chemistry Department, King Abdulaziz University , Jeddah, 21589 Saudi Arabia.

PMID: 26588736
DOI: 10.1021/ct300830k

Abstract

The governing parameters for the long-range intramolecular S-to-N acyl transfer in (S)-acyl isopeptides are shown by computational and statistical methods (principal component analysis and cluster analysis) to be driven by enthalpic and geometric effects over the range n = 5-20. The results emphasize the dependency of ΔG(‡) on the geometrical parameters governing the approach of the reactive termini and the importance of stabilizing intramolecular hydrogen bonds in the transition states (TSs), rather than the effects of TS ring-size. The competition between the intra- (uni-) and inter- (bi)molecular acyl transfers were studied for representative examples.