The H-bonding network of acylguanidine complexes: combined intermolecular (2h)J(H,P) and (3h)J(N,P) scalar couplings provide an insight into the geometric arrangement.
The H-bonding networks of arginines and acylguanidines are crucial for many biological and pharmaceutical interactions. However, the effect of acylation of guanidines on the binding mode and the H-bond strengths has not yet been explored in solution. Therefore, the H-bonding network of a (15)N labeled acylguanidine derivative in a bisphosphonate arginine receptor is investigated. The direct NMR detection of 1D, 2D, and 3D correlations caused by (2h)J(H,P) and, for the first time in nonbiomacromolecules, (3h)J(N,P) couplings, allows for the geometric analysis of the H-bonding network and indicates an end-on binding mode with two different POH angles. The acylguanidine adopts the same binding mode as the corresponding guanidine but forms significantly stronger H-bonds. This may explain the success of acylguanidine ligands in medicinal chemistry applications.
Federwisch
Guido
G
Institut fur Organische Chemie, Universitat Regensburg, Universitatsstrasse 31, D-93040 Regensburg, Germany.
Kleinmaier
Roland
R
Drettwan
Diana
D
Gschwind
Ruth M
RM
D000215:Acylation; D019791:Guanidine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure
D019791:Guanidine