Crystal and Molecular Structure of Aminoguanidine Sulphate, an Important Enzyme Inhibitor and Starting Material of Drug Syntheses

Abstract

Aminoguanidine is not only an agent with a variety of pharmacological effects but also an im portant starting material of am idinohydrazone-type drugs and enzyme inhibitors. There fore, we have now synthesized am inoguanidine sulphate CN4H 82+.S 0 42~ and determined its structure by single-crystal X-ray diffraction. The doubly protonated (dication) form o f am ino guanidine that is present in the sulphate could, in principle, exist in the form of several differ ent tautom ers. The crystal studied consisted exclusively of one tautomer: one of the nitrogens of the hydrazine moiety bears three hydrogen atoms while the other one (the one bound to the carbon) bears one hydrogen. The other two nitrogens are bound to two hydrogens each. The predominance of this tautom er can be explained by the very strong resonance in it. The dica tion of aminoguanidine is remarkably planar. The hydrogens of the hydrazine moeity are, however, clearly out of the plane of the other atoms. There is a strong hydrogen bond between the proton of the m onoprotonated nitrogen and one sulphate oxygen. This bond obviously causes the deviation of the hydrogen from the plane. The bonds between the carbon atom and the adjecnt nitrogens are essentially equally long, indicating that each bond has approxim ately the same am ount of double bond character. One of the positive charges of the dication is thus delocalized, being shared by all of the atoms of the C N 3 moiety. In this respect, the structure is similar to that of all bis(amidinohydrazones) whose structures have been determined. The other positive charge of aminoguanidine dication is localized at the nitrogen bearing three hydrogens.

Experimental and Computational Studies on Aminoguanidine Free Base, Monocation and Dication, Part I: The Crystal and Molecular Structure of Aminoguanidine Monohydrochloride and the ab Initio Structure of the Endiamine Tautomer of Aminoguanidine Free Base

“…16-31]. We have also reported the crystal and molecular structures of AG sulphate, CN4H 82+.S 0 42' [2] and dinitrate, CN4H 82+. (N 0 3")2 [1].…”

“…2. A list of measured interatom ic distances, bond angles and dihedral (torsion) angles is shown in Table II. Compound formula Mr Space group Crystal system W hen studied by single-crystal X-ray diffraction, the structure of AG monocation, as present in the crystals of AG monohydrochloride, is largely sim ilar to the structures of AG sulphate and dinitrate [1,2]. As compared to the dication in the latter, there is one hydrogen atom less attached to N1 in the monocation.…”

“…Comparison of the experimental structure of the monocation reported here and the experimentally determ ined structures reported for the dication in the solid state [1,2], with the calculated structures of the corresponding free molecule and molecular ions yields a way to forecast the structure of AG free base.…”

“…As the experimentally determined structures for AG dinitrate [1] and AG sulphate [2] seemed to suggest features that could shed light on the structure of this much de bated class of molecules, we have now also d eter mined the structure of AG monohydrochloride by single-crystal X-ray diffraction. These results in spired us to undertake a provisional com puta tional study of the AG free base and AG m onoca tion and dication, by quantum chemical methods based on ab initio molecular orbital theory [4] and density functional theory (DFT) [5], The readily available DFT methods implemented in Gaussian 94 [6] greatly facilitated this task.…”

“…We have previously studied aminoguanidine (AG) monocation and dication from an experi mental point of view [1][2][3]. As the experimentally determined structures for AG dinitrate [1] and AG sulphate [2] seemed to suggest features that could shed light on the structure of this much de bated class of molecules, we have now also d eter mined the structure of AG monohydrochloride by single-crystal X-ray diffraction.…”