Multiplicity of cadmium binding sites in nucleotides: X-ray evidence for the involvement of O21′ and O3′ as well as phosphate and N7 in inosine 5′-monophosphate

Abstract

Single-crystal X-ray methods have been used to characterize a hydrated polymeric cadmium derivative of inosine 51-monophosphate. In the structure there are two independent cadmium atoms, one of which binds to two ribose oxygen atoms, an N7 position on a base, and to three water molecules. The second metal atom binds to a phosphate oxygen, three water molecules, and to two N7 atoms, which are in cis-positions. For these last, the Cd-N bonds are appreciably out of the planes of the hypoxanthine bases so that the angle between these planes is only 31.40. IRODUCTIONDuring the past few years there has been increasing concern over the adverse effects on health of the build-up of heavy metals in the environment.Many of these are sparsely distributed in nature, but undesirable concentrations result from their use in industry and agriculture. One such toxic metal is cadmium, which is virtually absent in mammals at birth but which accumulates over a life-time 1,2Apart from localized high concentrations of cadmium in the atmosphere near industrial plant concerned with the refining of the metal or with electroplating, the most serious source of cadmium intake by the general population is thought to be food. Cadmium has been found in a wide range of 3 4 fresh and tinned foods , especially sea-foods We have recently been examining the interactions of metal ions with nucleic acid components in order to provide structural information concerning the binding sites of these metals. Such definitive information is useful for evaluating the possible influence of heavy metals on such processes as cell replication and, thereby, on the question of carcinogenicity or, conversely, anti-tumour activity (e.g., as with the platinum anti-tumour drugs5). As it has been suggested6'7 that occupational exposure to cadmium may increase the risk of cancer in man, and tumours have been induced in rats 1375

Magnesium – nucleotide interaction. Synthesis, structure, 1H, 13C nuclear magnetic resonance and Fourier transform infrared studies of Mg-inosine-5′-monophosphate complexes

“…The sodium ions in both IMPNaz and IMPHNa (16,17) are bound directly to O?.H and 03,H of the sugar hydroxyl groups and to four water molecules (no direct interaction with the phosphate group or the N7-atom of the base moiety exists here). The Cd(I1) and Ca(I1) cations are directly bound to the O,,H and O,.H hydroxyl groups as well as to the N7-site and the phosphate oxygen atoms in Cd2(IMP)3 -12H20 and Ca(IMP).6.5H20 compIexes (9,10). On comparison of the infrared spectra of the Na-, Cd-, and Ca-IMP compounds with the corresponding Ni and Co complexes they showed no metal-sugar interaction (6).…”

“…for Mgz(IMP)s. 15H20 (it should be noted that one of the IMP molecules is in the form of IMPNa2): C 25. 6.5H20 were prepared and recrystallized as reported (6)(7)(8)(9)(10).…”

“…I2H,O. One Mg(l1) ion binds to two N7-atoms and to a phosphate oxygen atom as well as to H,O molecules, whereas the second Mg(I1) ion is linked directly to the O,,H and O3.H sugar hydroxyl groups and to the N7-atom as well and to water molecules as in the case of Cd (9).…”

Metal-ribose binding in a transition-metal–nucleotide complex. Preparation and structure of a polymeric copper(II) complex of guanosine 2'-monophosphate

“…Only one complex is known in which the ribose hydroxyl functions are involved in coordination to a divalent metal ion, the polymeric [Cd2(5'-IMP)a-(H20)6] n, in which a multiplicity of metal-binding sites is observed, namely the ribose 0(2') and O(3') as well as phosphate O atoms and the base N(7) (Goodgame, Jeeves, Reynolds & Skapski, 1975). It might be supposed that the potential chelating site of the cis-diol 2',3'-hydroxy groups in the ribose residue of 5'-nucleotides would be competitive with the base N and phosphate and water O atoms in conditions of relatively low water content such as crystals, and in basic solutions, since the ribose hydroxy groups undergo deprotonation at about pH 12.5.…”

Crystallographic studies of interactions between nucleotides and metal ions. III. Two independent structural investigations of the polymeric complex of copper(II) with guanosine 5'-phosphate

“…Their sugar rings are puckered C(3')-endo (Jardetsky, 1960), the conformation about the C(4')-C(5') bond is gauchegauche (Shefter & Trueblood, 1965), the orientation of the base and sugar is anti (Sundaralingam & Jensen, 1965), and the purine rings assume a 'base-stacking' arrangement. On the other hand, the complexes Zn-IMP (de Meester, Goodgame, Jones & Skapski, 1974c), Cu-IMP (Aoki, 1977), Cd-IMP (Goodgame, Jeeves, Reynolds & Skapski, 1975a), cobalt--cytidine 5'-phosphate (Co-CMP) (Clark & Orbell, 1975), Zn-CMP (Aoki, 1976b), Mn-CMP (Aoki, 1976c), and Cd-CMP (Clark & Orbell, 1975;Goodgame, Jeeves, Reynolds & Skapski, 1975b;Bau, Gellert & Shiba, 1975) exhibit a variety of polymeric structures in which each metal ion is bonded to the base of one nucleotide and to phosphate groups of others, and some complexes assume an alternative C(2')-endo sugar pucker and some adopt base stacking while others do not. In addition, two platinum-nucleotide complexes, Pt-IMP (Goodgame, Jeeves, Phillips & Skapski, 1975) and Pt-CMP (Louie & Bau, 1977), have been reported; an IMP nucleotide molecule coordinates in a monodentate fashion through the base in the former, and a CMP nucleotide molecule acts as a bridging bidentate ligand via the base and a phosphate group, forming a dimeric structure with the C(2')-endo puckered sugars, in the latter.…”