CRYSTAL AND MOLECULAR-STRUCTURES OF THE FREE-BASE AND THE MONOHYDROCHLORIDE SALT OF THE ANTILEUKEMIC AGENT GLYOXAL BIS(AMIDINOHYDRAZONE) [GLYOXAL BIS(GUANYLHYDRAZONE)]

The first study on the crystal and molecular structures of basic forms of bis(amidinohydrazones) is reported. The structures of the free bas e and the monohydrochloride salt of the antileukemic agent glyoxal bis (amidinohydrazone) (GBG) were determined by single crystal X-ray diffr action and were refined to R-values of 0.038 and 0.040, respectively T hese structures are of special interest because recent results indicat e that, in contrast to previous assumptions, the free base may be the actual antileukemic form of bis(amidinohydrazones) and that the monoca tion form is the predominant species of antileukemic bis(amidinohydraz ones) at physiological conditions. In the crystals of the free base as well as in those of the monohydrochloride salt, GBG was found to exis t solely in the all-trans configuration of the chain and to consist of one of the three possible geometrical isomers only. In the solid stat e, GBG free base consists solely of the endiamine tautomer instead of the 'classical' carboximidamide tautomer, as does also the non-protona ted part of GBG monocation in the monohydrochloride salt. Proton NMR m easurements indicated that the free base consists of the endiamine tau tomer 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 betw een the mean planes of the molecules or the monocations is approximate ly 3.5 Angstrom. The crystals of the monohydrochloride salt contain on e molecule of water per each GBG monocation. In both compounds studied , the molecules in the crystals are held together by very extensive hy drogen bond networks and by the interaction of delocalized pi-electron s. The crystal of C4H10N8 is monoclinic, space group C2/c with a = 15. 874(6), b = 6.972(4), c = 7.813(5) Angstrom, beta = 90.34(4)degrees an d Z = 4. The crystal of C4H13N8OCl is monoclinic, space group P2(1)/n with a = 7.010(3), b = 22.307(9), c = 7.028(3) Angstrom, beta = 66.33( 3)degrees and Z = 4.