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Inorganic Biochemistry Volume 1
A Review of the Recent Literature Published Up to Late 1977
By H. A. O. Hill
The Royal Society of Chemistry
Copyright © 1979 The Chemical SocietyAll rights reserved.
ISBN: 978-1-84755-634-9
CHAPTER 1
Inorganic Analogues of Biological Molecules
C. A. McAULIFFE
1 Complexes of Amino-acids and Peptides
Of all the possible model studies of metal ions with biologically important ligands, those relating to metal-amino-acid interactions have been the longest studied ; the justification being,. of course, that proteins contain the same types of donor groups and the study of simple models is thus worthwhile. With the availability of peptides of increasing complexity, it has recently become possible to study much more complicated model systems. Of course, it should be borne in mind that amino-acids are interesting ligands in their own right. In this section the area is divided into three parts, namely metal complexes of (i) simple amino-acids and peptides; (ii) amino-acids containing sulphur donors; and (iii) amino-acids containing heterocyclic nitrogen donors.
Simple Amino-acids and Peptides. — It is not entirely clear what biological justification there is for studying chromium complexes of amino-acids, though there may be some relevance to the 'glucose tolerance factor'. Two lengthy studies have been reported. In one, the rather novel matrix method was used. This involves mixing hexamminechromium(III) nitrate with the amino-acid in 1:3 ratio in a mortar and then heating to 150 °C in an oven, or merely mixing the constituents in warm water. A large number of compounds were isolated with L-α-amino-acids (alanine, aminobutyric acid, norvaline, norleucine, valine, isoleucine, and leucine), viz. [Cr(ala)3], (+)-[Cr(am-but)3], [Cr(OH) (am-but)2]2,(+)- and (-)-[Cr(norval)3], (-)-[Cr(norleu)3], [Cr(isoleu)2(isoleu-O)(NH3)], (+)- and (-)-[Cr(leu)3] were prepared by the matrix method, and differences were noted 1 in the formation of the tris-type and the hydroxo-dimer complexes by the two methods. All of the tris-type complexes were of the fac structure. A number of complexes with L- and DL-asparagine, L- and DL-aspartic acid, L- and DL-glutamine, L- and DL-glutamic acid, L- and DL-lysine, and L-ornithine were also isolated, including a new complex of chromium(m) containing terdentate DL-aspartic acid and a species containing three different ligands (L-lysine, ammine, and water). A mixed salt of the (glycinato)bis(oxalato)chromate(III) complex has been prepared and characterized with the use of ion-exchange chromatography. In acidic media this complex has been shown to aquate to the cis-diaquabis(oxalato)chromate(III) ion. Formation constants of molybdenum(VI) and tungsten(VI) with aspartic and glutamic acids have been determined by the potentiometric method, and indicate that previous values are incorrect.
Very few iron-amino-acid complexes have been synthesized and studied. Holt and co-workers 6 have determined the crystal structure of tri-µ3-oxo-triaqua-hexakis(glycine)tri-iron(III) perchlorate, [Fe3O(glyH)s(H2O)3](ClO4)7, and have shown it to be similar to that of basic iron acetate, [Fe3O(CH3CO2)6(H2O)3]ClO4, with a trimeric unit having an oxygen atom at the centre. The remaining coordination sites of each iron are occupied by four carboxylate oxygens from bridging zwitterionic glycines and a single water molecule. This general area needs more study, especially by X-ray techniques. (See, for example the vast discrepancy in something as essential as calculated/found elemental analyses by Holt's group).
The synthesis, resolution of enantiomers, and rates of H exchange of Λ,Δ-α-(R,R,S,S) -[Co(trien)(glyOEt)Cl]2+ have been described, and structural assignments have been confirmed by an X-ray study of Λ,Δ-α-(R,R,S,S)-[Co(trien) -(glyO)]I2·3H2O. A series of mixed ligand cobalt(III)-Schiff base complexes with the general formula [Co{sal2-(S,S)-chxn}(aa)] (aa = glyH, L- and D-alaH, L-and D-valH, L- and D-leuH, L- and D-thrH, L- and D-trpH) are readily obtained from [Co{sal2-(S,S)-chxn}] and amino-acids by oxidation with air. All of these complexes adopt, stereoselectively, the Λ-cis-β1(fac)-structure, irrespective of the configuration of the amino-acids. On the other hand, the reactions of [Co-{sal2 -(S,S)-chxn}] with an excess of DL-amino-acids in open air gave [Co-{sal2 -(S,S)-chxn}(aa)], in which all L-amino-acids except proline are selectively co-ordinated. Higa and co-workers have published details of the separation and optical resolution of the isomers of bis(β-alaninato)(oxalato)cobalt(III) and (β-alaninato)(glycinato)(oxalato)cobalt(III) complexes. The synthesis of mixed ligand cobalt(III) complexes with (S)-aspartic-N-monoacetic acid, (S)-AMA, and different amino-acids Na[Co{(S)-AMA}(aa)] {aa = glyH, (R)- and (S)-alaH, valH, pheH, serH, and leuH} leads to a mixture of cis-N- and trans-N-isomers. The cis-N/trans-N interconversion of these compounds containing glycine and (R)- and (S)-leucine is further reported, 12 and it has been shown that the chirality of the bidentate amino-acidato species has a pronounced influence on the cis–trans equilibrium of these systems.
The oxidative rearrangement of dinuclear cobalt-dioxygen complexes to mononuclear cobalt(III) chelates in aqueous solution has been studied for the series of ligands glycylglycine, glycyl-L-alanine, glycyl-L-serine, L-serylglycine, L-alanyl-L-alanine, L-alanylglycine, and glycyl-L-tyrosine. The reaction proceeds in two first-order steps; the first is the more rapid (t1/2 [??] minutes), and it probably involves the oxidation of one ligand molecule per two cobalt atoms and the conversion of the bridging dioxygen moiety into water. The second step is slower (t1/2 [??] hours), and probably involves displacement of the oxidized ligand by the excess dipeptide present in solution.
Circular dichroism (c.d.) and proton magnetic resonance (1H n.m.r.) spectra of nickel(II) complexes containing a series of ethylenediamine-NN'-diacetic acids (H2edda) (see Figure 1), which are optically active quadridentate ligands, have been measured in aqueous solution. The epro complex, which contains L-proline residues on the ligand, is found to exhibit the same c.d. spectrum as complexes of other edda-type ligands containing L-alanine, L-valine, L-phenylalanine, and L-serine residues. These complexes stereospecifically take the Δ-S-cis-form in solution, and the large contact shift observed for the α-protons of the amino-acid moieties indicates that the substituent groups become axial to the chelate plane. Both 1H n.m.r. and e.p.r. spectroscopy have been used to deduce the structures of the complexes that are formed between nickel(II) or copper(II) and Thr-Lys-Ala-Ala in aqueous solution over a broad pH range. The binding sites in this tetrapeptide are —NH2 of threonine and three deprotonated nitrogens of the peptide linkages. A co-operative interaction was observed in the case of nickel(n) ions. A compound of the type [Ni(Bz-β-ala)2]·2H2O (Bz-β-ala = benzoyl-β-alaninate) and its amine adducts of the type [Ni(Bz-β-ala)2Bn]·xH2O (B = nitrogen base) have been reported. All of the complexes are hexaco-ordinate, and it is concluded that NiO6 and NiN6 chromophores exist for [Ni(Bz-β- ala)2]·2H2O and [Ni(en)2(Bz-β-ala)2], respectively.
Results of potentiometric titrations of [Pd(en)(H2O)2]2+ with glycylglycine (glyglyO) and glycinamide (glyNH2) are consistent· with equilibria (1) and (2), and similar conclusions have been . drawn about ·this system with L-asparagine and L-glutamine. 18 The palladium(II) complex of glycyl-L-aspartic acid forms monomeric and dimeric species with adenosine and ATP. At higher pH the palladium atom favours the N-1 over the N-7 co-ordination in nucleoside and nucleotide molecules. At pH > 10 adenosine is unbound, and promotes a 'double' hydrolysis of the Pd-dipeptide complex. The ATP forms much more stable complexes than adenosine, and even at pH values > 10 in 2: 1 solution the Pd–N-1 species is the dominant one (80% of ATP). Platinum(n) complexes containing (S,S)- or (R,R)-trans-2-butene and various L-amino-acids, e.g. cis(N, olefin)-[PtCl(L-prolinate){(S,S)-trans-2-butene}], have been synthesized and olefin inversion has been studied.
Regardless of the molar ratio of salicylaldehyde to L-arginine, a 1:1 Schiff base (1) is obtained, i.e. N-salicylidenearginine, L. Infrared and electronic spectra and magnetic susceptibility measurements from 80 to 300 K for the complexes [Cu(L)NO3], [Cu(L)Cl]·2H2O, [Ni(L)NO3], and [Ni(L)Cl]·H2O indicate that the copper nitrate complexes are antiferromagnetic (TN = 250 K), and a tetrameric structure has been proposed. The chloride appears to be a mixture of the same tetrameric species and a magnetically dilute form which may be dimeric. Low magnetic moments suggest that the nickel complexes are mixtures of octahedral and planar ones. Hatfield and co-workers have reported electronic structures of [CuL2] complexes (L = anion of L-asparagine or DL-α-amino-n-butyric acid).
Gergely and Nagypál report the stoicheiometries, stability constants, and the enthalpies and entropies of formation of the complexes formed in the systems of copper(II) with glycylglycine, glycyl-DL-α-alanine, DL-α-alanylglycine, and DL-α-alanyl-DL-α- alanine, and conclude that there is no possibility of the formation of [CuL2] and [Cu(L2H-2)]2- (L = dipeptide anion, or H2NCHR1CONHCHR2CO2-). Further studies are reported for thirty-nine equilibrium systems involving mixed dipeptide-aminoacid complexes of copper(n), and from the high relative stabilities of the mixedligand complexes containing α-alanine and aspartic acid it seems that the aminoacids occupy one equatorial and one axial site around the metal. May et al. have computed the distribution of Cu2+, and of divalent Ca, Mg, Mn, Zn, Pb, and Fe3+, amongst 5000 complexes formed with 40 ligands in a simulation of metal ion equilibria in 'biofiuids'. Correlation of the stereochemical differences of the copper(II) and nickel(II) complexes of the diastereoisomeric dipeptides L-alanyl-L-alanine, D-alanyl-L-alanine, L-leucyl-L-tyrosine, and D-leucyl-L-tyrosine with their different aqueous equilibrium constants indicates that the hydrophobic nature of the side-chains plays an important part in both conformation and equilibria. pH titration data have afforded equilibrium constants for divalent copper and zinc complexes of glycylglycyl-L-histidine, Gly-Gly-His-Gly-Gly, their alkyl esters, and their benzyloxycarbonyl derivatives. The copper-peptide complexes are reasonable models for the binding of Cu2+ by albumin, but the disparity between constants for zinc–peptide and –albumin complexes indicates that a different binding site is involved.
The therapeutic implications of the study of metal–amino-acid complexes must be mentioned. Thus, the perfusion of intact cat skin by a saline solution of bis(glycinato)copper(II) that is labelled with 64Cu has been studied in a diffusion cell, and such work is relevant to the solubility of metallic copper in human sweat and to the possible therapeutic value of the 'copper bracelet'. Equilibrium-dialysis studies of the ternary systems albumin–copper(II)–ligand (ligand = 3, 6-diazaoctane-1,8-diamine or D-penicillamine) have been carried out in dilute NaCl solution to measure the amounts of low-molecular-weight membranediffusable copper(II) species formed. There is a substantial difference between the two ligands in this respect which correlates with their different clinical behaviour when used in the treatment of patients with Wilson's disease. 29 Other ternary systems have been examined, viz. formation constants of [Cu(DL-histidinate) (L-amino-acidate)], and the optical resolution of DL-aspartic acid and of DL- glutamic acid has been achieved via the formation of ternary complexes of cupric complexes of these ligands and L-arginine, L-lysine, or Lornithine. 31 Detailed investigations of the influence of glycine, alanine, histidine, glycylglycine, imidazole, and 1,10-penanthroline on the Cu2+-catalysed rates of decarboxylation and enolization of oxaloacetate have been performed. Calculations show that many of the differences observed between the metal-ion-catalysed enzymatic and the nonenzymatic decarboxylation of oxac2- can be accounted for almost entirely by increases in the stabilities of the known complexes in the environment presented by the enzyme (the low-dielectric region at the active site of the enzyme?). Other metal-ion-promoted (e.g. Cu2+, Ni2+, Zn 2+, Co2+) hydrolyses of amino-acid esters have been studied.
Numerous copper-containing proteins utilize molecular oxygen in respiratory and biosynthetic functions, but there are few well-characterized copper complexes bound to small molecules. The four-co-ordinate copper(1) complex difluoro-3, 3'-(trimethylenedinitrilo)-bis(2-butanone oximato)borate copper(I) can be produced by electrochemical reduction of the corresponding copper(II) species. The copper(I) derivative binds unidentate ligands (e.g. CO, 1-methylimidazole, or MeCN) to yield pentaco-ordinate adducts. The carbonyl derivative is square-pyramidal, with Cu displaced 96 pm out of the basal nitrogen plane; Cu — CO = 178 pm. Electrode potentials have been measured for forty cuIII,II-peptide couples (including peptide amides) in aqueous solution. These potentials (1.02 — 0.45 V) are very sensitive to changes in the nature of the ligand, and decrease with an increase in the number of deprotonated peptide groups. The triply deprotonated peptide and the highly C-substituted tripeptide complexes have effective potentials at physiological pH such that oxidation by O2 to CuIII is possible. Similar studies for thirty NiIII,II–peptide couples have been reported.
The crystal and molecular structures of L-prolinatodiphenylboron and L-prolinatodimethylgallium have been obtained, and Zuckerman has synthesized diglycinatotin(II), dimethyltin(IV) diglycinate, and dimethyltin(IV) di-α-alaninate. Circular polarized emission (CPE) and total emission (TE) spectra for Eu3+ and Tb3+ complexes of L-aspartic acid, L-serine, L-threonine, and L-histidine in D2O solution have been measured, and spectral parameters can be correlated with ligand-lanthanide ion binding characteristics.
The free radical 4-amino-2,2,6,6-tetramethylpiperidinyl-1-oxyl (ATMPO) forms cis-[Pt(ATMPO)2(NO3)2], and the latter has been used to label poly(L- glutamate), and poly(L-aspartate) and poly(L-lysine); labelling occurs by the displacement of nitrate by polymer side-chains. E.s.r. spectra of labelled (Glu)n are anisotropic, and monitor the helix–coil transition and polymer aggregation. The Pt is probably bifunctionally anchored to adjacent carboxylate groups. Crystals of [cyclo(-L-Pro-Gly-)4RbSCN·3H2O]2 have been obtained from rubidium thiocyanate and the cyclic octapeptide cyclo(L-prolylglycyl)4 in H2O–Me2CO. The rubidium cation has a distorted octahedral environment consisting of four glycyl carbonyl oxygens from one cyclic peptide of the dimer, one glycyl carbonyl oxygen from the other cyclic peptide of the dimer, and one oxygen from a water molecule. Such studies are of relevance to ion transport across membranes, and cyclic peptides themselves possess potent biological activities as antibiotics, toxins, and hormones. This same cyclo(L-prolylglycyl)4 forms complexes of 1:2 and 1: 1 cation-peptide stoicheiometries with a variety of alkali-metal and alkaline-earth cations. The larger cations, Cs+ and Ba2+, have binding constants comparable to those with naturally occurring cyclic peptides. The synthesis of cyclo(-L-Val-Gly-L-Pro-)3 (2) has been achieved. This homodetic cyclic dodecapeptide contains only naturally occurring amino-acids and is a model of an ion carrier that is related to valinomycin. The stabilities of some 1:1 complexes can be correlated with the diameter of the cation, viz. Mg2+ [much less than] Ca2+ [much less than] Ba2+. The binding of copper(II) to some poly(α-amino-acids) has been reported.
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Excerpted from Inorganic Biochemistry Volume 1 by H. A. O. Hill. Copyright © 1979 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
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Table of Contents
Contents
Chapter 1 Inorganic Analogues of Biological Molecules By C. A. McAuliffe, 1,Chapter 2 Inorganic Analogues of Biological Processes By B. T. Golding and G. J. Leigh, 35,
Chapter 3 Storage, Transport, and Function of Non-transition Elements By M. N. Hughes, 88,
Chapter 4 Storage and Transport of Transition-metal Ions By P. M. Harrison and A. Treffry, 120,
Chapter 5 Oxygen-transport Proteins By M. Brunori, B. Giardina, and J. V. Bannister, 159,
Chapter 6 Electron-transport Proteins By C. Greenwood and D. Barber, 210,
Chapter 7 Oxidases and Reductases By B. E. Smith and P. F. Knowles, 271,
Chapter 8 Metalloenzymes By A. Galdes and H. A. O. Hill, 317,
Chapter 9 Inorganic Elements in Biology and Medicine By N. J. Birch and P. J. Sadler, 356,
Author Index, 421,