2D-NMR Studies on Bis(Amidinohydrazones). I. A Proton-Carbon Heteronuclear Shift Correlation Study on the Enzyme Inhibitors Methylpropylglyoxal Bis(Amidinohydrazone) and Butylmethylglyoxal Bis(Amidinohydrazone)

Abstract

The first 2D-NMR study on bis(amidinohydrazones) [‘(guanylhydrazones)’] is reported. Heteronuclear shift correlation (HETCOR) experiments were performed on the enzyme inhibitors methylpropylglyoxal bis(amidinohydrazone) (MPGBG) and butylmethylglyoxal bis(amidinohydrazone) (BMGBG). The results obtained made possible the unambiguous assignment of the previously unassigned resonances of the side-chain carbon atoms of MPGBG. The results indicate that the chemical shifts of the protons of the propyl side chain of MPGBG are positively correlated to the ¹³C chemical shifts of the corresponding carbon atoms. The chemical shifts of the carbon atoms of the propyl side chain decrease as a function of the position of the atom in the side chain, the terminal methyl group having the lowest shift value. These results are in full agreement with previous results on the analogous compound dipropylglyoxal bis(amidinohydra- zone), whose side-chain carbon resonances were assigned using totally different techniques. In the case of BMGBG, however, HETCOR contour plots clearly indicate that there is no correlation between the chemical shifts of the protons of the butyl side chain and the 13C chemical shifts of the corresponding carbons. Because the 200 MHz proton spectrum of BMGBG is not fist-order, only the 1 3 resonance∼ of the methyl substituent and the resonances of carbons 1 and 4 (but not those of carbons 2 and 3) of the butyl side chain could be assigned on the basis of the HETCOR study. Yet, the results gave a rough estimate of the previously unknown chemical shifts of the protons bound to butyl carbon atoms 2 and 3.

Key Words:

• Adenosylmethionine Decarboxylase Inhibitors
• Bis(guanylhydrazones)
• Carbon-13 NMR Spectroscopy
• Chemical Shift Assignment
• Polyamine Antimetabolites
• Substituent Effects