Crystal and Molecular Structures of the Free Base and the Monohydrochloride Salt of the Antileukemic Agent Glyoxal bis(Amidinohydrazone) [`Glyoxal bis(Guanylhydrazone)’

Abstract

The first study on the crystal and molecular structures of basic forms of bis(amidinohydrazones) is reported. The structures of the free base and the monohydrochloride salt of the antileukemic agent glyoxal bis(amidinohydrazone) (GBG) were determined by single crystal X-ray diffraction and were refined to R-values of 0.038 and 0.040, respectively. These structures are of special interest because recent results indicate that, in contrast to previous assumptions, the free base may be the actual antileukemic form of bis(amidinohydrazones) and that the monocation form is the predominant species of antileukemic bis(amidinohydrazones) at physiological conditions. In the crystals of the free base as well as in those of the monohydrochloride salt, GBG was found to exist solely in the all-trans configuration of the chain and to consist of one of the three possible geometrical isomers only. In the solid state, GBG free base consists solely of the endiamine tautomer instead of the 'classical’ carboximidamide tautomer, as does also the non-protonated part of GBG monocation in the monohydrochloride salt. Proton NMR measurements indicated that the free base consists of the endiamine tautomer also in dimethyl sulfoxide solution. In the solid state, both of the compounds studied consist of stacks of planes. In the case of the free base, the stacks are crisscross to each other. The distance between the mean planes of the molecules or the monocations is approximately 3.5 Å. The crystals of the monohydrochloride salt contain one molecule of water per each GBG monocation. In both compounds studied, the molecules in the crystals are held together by very extensive hydrogen bond networks and by the interaction of delocalized π-electrons. The crystal of C4H10N8 is monoclinic, space group C2/c with a = 15.874(6), b = 6.972(4), c = 7.8l3(5)Å, β = 90.34(4)° and Z = 4. The crystal of C4H13N8OC1 is monoclinic, space group P21/n with α = 7.010(3), b = 22.307(9), c = 7.028(3)Å, β = 66.33(3)° and Ζ = 4.