-
[show abstract]
[hide abstract]
ABSTRACT: For elucidating the mechanism of the general acid/base catalysis of the hydrolysis of RNA phosphodiester bonds, a number of cleaving agents having two cyclen moieties tethered to a 1,3,5-triazine core have been prepared and their ability to bind and cleave uridylyl-3',5'-uridine (UpU) studied over a wide pH range. Around neutral pH, the cleaving agents form a highly stable ternary complex with UpU and Zn(II) through coordination of the uracil N3 and the cyclen nitrogen atoms to the Zn(II) ions. Under conditions where the triazine core exists in the deprotonated neutral form, hydrolysis of UpU, but not of adenylyl-3',5'-adenosine (ApA), is accelerated by approximately two orders of magnitude in the presence of the cleaving agents, suggesting general base rather than metal ion catalysis. The probable mechanism of the observed catalysis and implications to understanding the general acid/base-catalyzed phosphodiester hydrolysis by ribozymes are discussed.
Dalton Transactions 02/2012; 41(11):3328-38. · 3.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The Cu,Zn superoxide dismutases (Cu,Zn SOD) isolated from some Gram-negative bacteria possess a His-rich N-terminal metal binding extension. The N-terminal domain of Haemophilus ducreyi Cu,Zn SOD has been previously proposed to play a copper(II)-, and may be a zinc(II)-chaperoning role under metal ion starvation, and to behave as a temporary (low activity) superoxide dismutating center if copper(II) is available. The N-terminal extension of Cu,Zn SOD from Actinobacillus pleuropneumoniae starts with an analogous sequence (HxDHxH), but contains considerably fewer metal binding sites. In order to study the possibility of the generalization of the above mentioned functions over all Gram-negative bacteria possessing His-rich N-terminal extension, here we report thermodynamic and solution structural analysis of the copper(II) and zinc(II) complexes of a peptide corresponding to the first eight amino acids (HADHDHKK-NH(2), L) of the enzyme isolated from A. pleuropneumoniae. In equimolar solutions of Cu(II)/Zn(II) and the peptide the MH(2)L complexes are dominant in the neutral pH-range. L has extraordinary copper(II) sequestering capacity (K(D,Cu)=7.4×10(-13)M at pH 7.4), which is provided only by non-amide (side chain) donors. The central ion in CuH(2)L is coordinated by four nitrogens {NH(2),3N(im)} in the equatorial plane. In ZnH(2)L the peptide binds to zinc(II) through a {NH(2),2N(im),COO(-)} donor set, and its zinc binding affinity is relatively modest (K(D,Zn)=4.8×10(-7)M at pH 7.4). Consequently, the presented data do support a general chaperoning role of the N-terminal His-rich region of Gram-negative bacteria in copper(II) uptake, but do not confirm similar function for zinc(II). Interestingly, the complex CuH(2)L has very high SOD-like activity, which may further support the multifunctional role of the copper(II)-bound N-terminal His-rich domain of Cu,Zn SODs of Gram-negative bacteria. The proposed structure for the MH(2)L complexes has been verified by semiempirical quantum chemical calculations (PM6), too.
Journal of inorganic biochemistry 09/2011; 106(1):10-8. · 3.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Copper(II) and nickel(II) binding properties of two pseudo tetrapeptides, N-Boc-Gly-Gly-Gly-Histamine (BGGGHa) and Gly-Gly-Gly-Histamine (GGGHa) have been investigated by pH-potentiometric titrations, UV-visible-, EPR-, NMR- and ESI-HRMS (electrospray ionization high resolution MS) spectroscopies, in order to compare the role of N-terminal amino group and imidazole moiety at the fourth position in the complex formation processes. Substantially higher stabilities were determined for the ML complexes of GGGHa, compared to those of BGGGHa, supporting the coordination of the terminal amino group and the histamine imidazole of the non-protected ligand. A dimeric Cu(2)H(-2)L(2) species, formed through the deprotonation of peptide groups of the ligands, was found in the GGGHa-copper(II) system. Deprotonation and coordination of further amide nitrogens led to CuH(-2)L and, above pH~10, CuH(-3)L. Experimental data supports a {NH(2), 2 × N(amide),N(im)} macrochelate structure in CuH(-2)L whereas a {NH(2), 3 × N(amide)} coordination environment in CuH(-3)L. The first two amide deprotonation processes were found to be strongly cooperative with nickel(II) and spectroscopic studies proved the transformation of the octahedral parent complexes to square planar, yellow, diamagnetic species, NiH(-2)L and above pH~9, NiH(-3)L. In the basic pH-range deprotonation and coordination of the amide groups also took place in the BGGGHa containing systems, leading to complexes with a {3 × N(amide),N(im)} donor set, and in parallel the re-dissolving of precipitate. Above pH~11, a further proton release from the pyrrolic NH group of the imidazole ring of BGGGHa occurred providing an additional proof for the different binding modes of the two ligands.
Journal of inorganic biochemistry 01/2011; 105(1):92-101. · 3.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The speciation of organotin(IV) cations in natural waters, in sewage or in biofluids is strongly influenced by the complex formation with the available metal-binding compounds, i.e., both high and low molecular weight ligands of biological and environmental interest. The primary intention of this chapter is to discuss the aquatic solution chemistry of organotin cations and their complexes formed with low and high molecular weight bioligands. Besides, some synthetic aspects, applications and sources of organotin pollution, their destinations in the environment, and toxicology will be also shortly discussed.
Metal ions in life sciences. 01/2010; 7:111-51.
-
[show abstract]
[hide abstract]
ABSTRACT: The zinc(II) and copper(II) binding ability of two oligopeptide fragments, Ac-HHPHG-NH(2) and Ac-HHPHGHHPHG-NH(2), derived from the repeat-region of the His-Pro-rich domain of histidine-rich glycoprotein (HRG) and the structure of the formed complexes have been investigated by potentiometry, NMR-, UV-visible-, CD-, SRCD- and EPR spectroscopy. Exclusive coordination of the side-chain imidazoles of the peptides has been observed with both metal ions in the acidic and neutral pH range. While the three His units of the pentapeptide resulted in a modest stability of the ML complexes, the decapeptide with its increased number of His residues offered a high-affinity metal binding site for both metal ions with the participation of at least four nitrogen donors. Due to the high number of potential donor groups, the formation of binding isomers of the protonated and parent complexes is very likely. Both peptides show a synchrotron radiation (SR) CD-pattern resembling to that of the polyproline II structure, similarly to that of the His-Pro-rich domain of the HRG protein. The longer sequence was shown to bind a second metal ion in the slightly acidic pH-range. The determined stability data suggest a remarkable extra stabilization emerging in the decapeptide for the coordination of the second metal ions, as compared to the ML complexes of the pentapeptide. Whether the observed cooperativity has similarities to the cooperative metal binding feature of HRG or the two phenomena have different sources is a question yet to be clarified.
Journal of inorganic biochemistry 09/2009; 103(12):1634-43. · 3.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A histidine-rich peptide HSHRDFQPVLHL-NH(2) (L), identical with the N-terminal fragment of the anti-angiogenic human endostatin has been synthesized. Endostatin is a recently identified broad spectrum angiogenesis inhibitor, which inhibits 65 different tumor types. The N-terminal 25-mer peptide fragment of human endostatin has the same antitumor effect as the entire protein. The zinc(II) binding is crucial for the antitumor effect in both cases. Our peptide may provide all critical interactions for zinc(II) binding present in the N-terminal 25-mer peptide fragment. In addition, the N-terminus of human endostatin has a supposedly high affinity binding site for copper(II), similar to human serum albumin. Since copper(II) is intimately involved in angiogenesis, this may have biological relevance. In order to determine the metal binding properties of the N-terminal fragment of endostatin, we performed equilibrium, UV-visible (UV-vis), CD, EPR and NMR studies on the zinc(II) and copper(II) complexes of L. In the presence of zinc(II) the formation of a stable [NH(2),3N(im),COO(-)] coordinated complex was detected in the neutral pH-range. This coordination mode is probably identical to that present in the zinc(II) complex of the above mentioned N-terminal 25-mer peptide fragment of human endostatin. Moreover, L has extremely high copper(II) binding affinity, close to those of copper-containing metalloenzymes, and forms albumin-like [NH(2),N(-),N(-),N(im)] coordinated copper(II) complex in the neutral pH-range, which may suggest that copper(II) binding is involved in the biological activity of endostatin.
Journal of inorganic biochemistry 05/2009; 103(7):940-7. · 3.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The peptides Ac-His-Pro-His-Pro-His-NH(2) (L1) and Ac-Lys-His-Pro-His-Pro-His-Gln-NH(2) (L2) have been prepared and the equilibria of their proton, copper(II) and zinc(II) complexes in aqueous solution have been studied by the combination of pH-potentiometric titrations, UV/visible and circular dichroism (CD) spectroscopy. The latter methods also provided information on solution structure of the complexes formed under different conditions. Both ligands formed complexes with three imidazole nitrogens around the metal ion at pH ~7. In the L1 containing system precipitation of either copper(II) or zinc(II) complexes occurred upon slight increase of the pH. The re-titration of the filtered and acidified precipitates revealed that the insoluble materials were neutral complexes rather than metal-hydroxides. Indeed, by attaching amino acids with polar side-chains to the His-Pro-His-Pro-His template in L2 we could prevent any precipitation, and the soluble complexes around pH ~7 exerted three imidazole nitrogens and a (deprotonated) water molecule around the metal ions. To our knowledge L2 provides the first example of a short peptide preventing both the amide nitrogen coordination in copper(II) and the formation of copper(II) and zinc(II) hydroxides. The zinc(II) and copper(II) complexes at pH ~7 having similar structure to the natural hydrolytic and redox enzymes, respectively, showed considerable activity in hydrolytic cleavage assays with a model substrate (2-hydroxypropyl-4-nitrophenyl phosphate), as well as with native plasmid DNA, and in a superoxide dismutase-like reaction.
Dalton Transactions 01/2009; · 3.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The copper(II), nickel(II) and zinc(II) binding ability of the multi-histidine peptide N-acetyl-His-Pro-His-His-NH(2) has been studied by combined pH-potentiometry and visible, CD and EPR spectroscopies. The internal proline residue, preventing the metal ion induced successive amide deprotonations, resulted in the shift of this process toward higher pH values as compared to other peptides. The metal ions in the parent [ML](2+) complexes are exclusively bound by the three imidazole side chains. In [CuH(-1)L](+), formed between pH 6-8, the side chains of the two adjacent histidines and the peptide nitrogen between them are involved in metal ion binding. The next deprotonation results in the proton loss of the coordinated water molecule (CuH(-1)L(OH)). The latter two species exert polyfunctional catalytic activity, since they possess superoxide dismutase-, catecholase- (the oxidation of 3,5-di-tert-butylcatechol) and phosphatase-like (transesterification of the activated phosphoester 2-hydroxypropyl-4-nitrophenyl phosphate) properties. On further increase of the pH rearrangement of the coordination sphere takes place leading to the [CuH(-3)L](-) species, the deprotonated amide nitrogen displaces a coordinated imidazole nitrogen from the equatorial position of the metal ion. The shapes of the visible and CD spectra reflect a distorted arrangement of the donor atoms around the metal ion. In presence of zinc(II) the species [ZnL](2+) forms only above pH 6, which is shortly followed by precipitation. On the other hand, the [NiL](2+) complex is stable over a wide pH range, its deprotonation takes place only above pH 8. At pH 10 an octahedral NiH(-2)L species is present at first, which transforms slowly to a yellow square planar complex.
Journal of inorganic biochemistry 08/2008; 102(7):1438-48. · 3.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The ability of the dinuclear Zn2+ complex of 1,4-bis[(1,5,9-triazacyclododecan-3-yloxy)methyl]benzene (L(1)) to promote the cleavage of the phosphodiester bond of dinucleoside-3',5'-monophosphates that contain a guanine base has been studied over a narrow pH range from pH 5.8 to 7.2 at 90 degrees C. Comparative measurements have been carried out by using the trinuclear Zn2+ complex of 1,3,5-tris[(1,5,9-triazacyclododecan-3-yloxy)methyl]benzene (L(2)) as a cleaving agent and guanylyl-3',5'-guanosine (5'-GpG-3') as a substrate. The strength of the interaction between the cleaving agent and the starting material has been elucidated by UV spectrophotometric titrations. The speciation and binding mode have been clarified by potentiometric titrations with hydrolytically stable 2'-O-methylguanylyl-3',5'-guanosine and 1H NMR spectroscopic measurements with guanylyl-3',5'-guanosine. The results show that the guanine base is able to serve as a site for anchoring for the Zn2+-azacrown moieties of the cleaving agents L(1) and L(2), analogously to uracil base. The interaction is, however, weaker than with the uracil base and, hence, only the 5'-GpG-3' site (in addition to 5'-GpU-3' and 5'-UpG-3' sites) is able to markedly modulate the phosphodiester cleavage by the Zn2+ complexes of di- and trinucleating azacrown ligands containing an ether oxygen as a potential H-bond-acceptor site.
ChemBioChem 08/2008; 9(11):1739-48. · 3.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The Cu,Zn superoxide dismutase (Cu,ZnSOD) isolated from Haemophilus ducreyi possesses a His-rich N-terminal metal binding domain, which has been previously proposed to play a copper(II) chaperoning role. To analyze the metal binding ability and selectivity of the histidine-rich domain we have carried out thermodynamic and solution structural analysis of the copper(II) and zinc(II) complexes of a peptide corresponding to the first 11 amino acids of the enzyme (H(2)N-HGDHMHNHDTK-OH, L). This peptide has highly versatile metal binding ability and provides one and three high affinity binding sites for zinc(II) and copper(II), respectively. In equimolar solutions the MHL complexes are dominant in the neutral pH-range with protonated lysine epsilon-amino group. As a consequence of its multidentate nature, L binds zinc and copper with extraordinary high affinity (K(D,Zn)=1.6x10(-9)M and K(D,Cu)=5.0x10(-12)M at pH 7.4) and appears as the strongest zinc(II) and copper(II) chelator between the His-rich peptides so far investigated. These K(D) values support the already proposed role of the N-terminal His-rich region of H. ducreyi Cu,ZnSOD in copper recruitment under metal starvation, and indicate a similar function in the zinc(II) uptake, too. The kinetics of copper(II) transfer from L to the active site of Cu-free N-deleted H. ducreyi Cu,ZnSOD showed significant pH and copper-to-peptide ratio dependence, indicating specific structural requirements during the metal ion transfer to the active site. Interestingly, the complex CuHL has significant superoxide dismutase like activity, which may suggest multifunctional role of the copper(II)-bound N-terminal His-rich domain of H. ducreyi Cu,ZnSOD.
Journal of inorganic biochemistry 06/2008; 102(9):1700-10. · 3.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The equilibrium and solution structural properties of the iron(III) and copper(II) complexes of an asymmetric salen-like ligand (N,N'-bis(2-hydroxybenzyl)-2,3-diamino-propionic acid, H(3)bhbdpa) bearing a pendant carboxylate group were characterized in aqueous solution by potentiometric, pH-dependent electron paramagnetic resonance (EPR) and UV-Vis (UV-Visible) measurements. In the equimolar systems the pentadentate ligand forms very stable, differently protonated mononuclear complexes with both metal ions. In the presence of iron(III) {NH, PhO(-), COO(-)}, {2NH, 2PhO(-), COO(-)} and {2NH, 2PhO(-), COO(-), OH(-)} coordinated complexes are dominant. The EPR titrations reflected the presence of microscopic complex formation pathways, leading to the formation of binding isomers in case of Cu(H(2)bhbdpa)(+), Cu(Hbhbdpa) and Cu(bhbdpa)(-). The {2NH, 2PhO(-)+COO(-)/H(2)O} coordinated Cu(bhbdpa) is the only species between pH 6-11. At twofold excess of metal ion dinuclear complexes were detected with both iron(III) and copper(II). In presence of iron(III) a mu-carboxylato-mu-hydroxo-bridged dinuclear complex (Fe(2)(bhbdpa)(OH)(3)) is formed from Fe(H(2)bhbdpa)(2+) through overlapping proton release processes, providing one of the rare examples for the stabilization of an endogenous carboxylate bridged diiron core in aqueous solution. The complex Cu(2)(bhbdpa)(+) detected in the presence of copper(II) is a paramagnetic (S=1) species with relatively weakly coupled metal ions.
Journal of Inorganic Biochemistry 08/2005; 99(7):1480-9. · 3.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Copper(II) and zinc(II) complexes of a polyamino-polyol ligand 1,3,5-trideoxy-1,3,5-tris(methylamino)-cis-inositol (tmci) have been investigated as potential candidates for the selective elimination of the 5'-cap structure of mRNA. A cap-model compound ApppA has been utilised as substrate for studying the effect of the different metal ion complex catalysts on the hydrolysis of the triphosphate bridge. Kinetic experiments have been performed by the variation of pH, metal-to-ligand ratio and total concentrations of the metal ion and ligand. The zinc(II) complexes of tmci have been proved to possess a remarkable activity for the hydrolysis of ApppA. The observed rate enhancement compared to the uncatalysed reaction was found to be 12,000-fold, in the presence of 4.5mM zinc(II) and 1.5mM tmci at pH approximately 7.5. In contrast with the copper(II) containing systems, an extra product has also been formed during the cleavage process, beside the expected AMP and ADP. According to the ESI-MS characterisation of the samples, the additional product is a covalent phosphoester adduct of AMP and the ligand. The formation of this species is initiated by a nucleophilic attack of a zinc(II)-bound alcohol or alkoxo group on one of the alpha phosphate groups of ApppA, which leads to the formation of a phosphodiester bond. In an alternative pathway, the substrate is cleaved into AMP and ADP. According to the pH-potentiometric studies, performed with the tmci-zinc(II) system, di- and trinuclear complexes are responsible for the accelerated ApppA hydrolysis. The copper(II)-tmci 2:1 system showed only a modest kinetic activity. The rate acceleration significantly increased when threefold excess of copper(II) was applied. Although, the detailed investigations above pH approximately 6.6 have been prevented by precipitate formation during the addition of the substrate into the reaction solution, the activity of the copper(II)-tmci 3:1 system does not exceed that of the zinc(II) complexes. Due to the specific mechanism leading to the covalent extra product, the zinc(II) complexes of tmci provide a comparable rate enhancement for ApppA hydrolysis to the widely studied lanthanide or copper(II) species, in spite of the fact that they are stronger Lewis acids.
Journal of Inorganic Biochemistry 07/2005; 99(6):1283-93. · 3.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The equilibria and solution structure of complexes formed between copper(II) and carcinine (beta-alanyl-histamine) at 2< or = pH< or =11.2 have been studied by EPR and NMR relaxation methods. Beside the species that have already been described in the literature from pH-potentiometric measurements, several new complexes have been identified and/or structurally characterized. The singlet on the EPR spectrum detected in equimolar solutions at pH 7, indicates the formation of an oligomerized (CuL)n(2n+) complex, with [NH2,Nim] coordination. The oligomerization is probably associated with the low stability of the ten-membered macrochelate ring, which would form in the mononuclear complex CuL2+. In presence of moderate excess of ligand the formation of four new bis-complexes (CuL2Hn(2+n), n=2,1 and 0/-1) was detected with [Nim][Nim], [NH2,Nim][Nim] and [NH2,N-,Nim][Nim] type co-ordination modes, respectively. At higher excess of ligand ([L]/[Cu2+]>10) and at pH approximately 7, the predominant species is CuL4H2(4+). The 1H and 13C relaxation measurements of carcinine solutions (0.6 M) in presence of 0 mM< or = [Cu2+](tot)< or = 5 mM at pH=6.8, allowed us to extract the carbon-to-metal distances, the electronic relaxation and tumbling correlation times, as well as the ligand exchange rate for the species CuL4H2(4+). According to these results, the metal ion is [4Nim] co-ordinated in the equatorial plane, while the neutral amino groups are unbounded. Since naturally occurring carcinine shows in vivo antioxidant property, the SOD-like activity of the copper(II)-carcinine system has also been investigated and the complex CuLH(-1) was found to be highly active.
Journal of Inorganic Biochemistry 12/2004; 98(12):1995-2005. · 3.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The ability of the dinuclear complexes of tdci [1,3,5-trideoxy-1,3,5-tris(dimethylamino)-cis-inositol] to promote the cleavage of the phosphodiester bonds of nucleoside 2',3'-cyclic monophosphates, dinucleoside monophosphates and polyribonucleotides has been studied. The homodinuclear copper(II) and zinc(II) complexes efficiently promote the hydrolysis of cyclic nucleotides. The second-order rate constant (k(2) approximately 0.44 M(-1) s(-1)) estimated for the cleavage of 2',3'-cAMP induced by dinuclear copper(II) complexes is about 107 times greater than that for the hydroxide-ion-catalysed reaction. The complex selectively cleaves the 2'O-P bond of 2',3'-cUMP and forms the 3'-product in 91 % yield. An equimolar mixture of copper(II), zinc(II) and tdci proved to be more efficient than either of the binary systems: a 7-20-fold rate enhancement was observed for the cleavage of 2',3'-cNMP substrates. The half-life for the hydrolysis of 2',3'-cAMP decreased from 300 days to five minutes at 25 degrees C when the concentration of each of the three components was 2.5 mM. In contrast to the copper(II) or zinc(II) complexes of tdci, the heterodinuclear species promoted the hydrolysis of several dinucleoside monophosphates. For two ApA isomers, cleavage of the 3',5'-bond was about 6.5 times faster than cleavage of the 2',5'-bond. On the basis of the kinetic data, a trifunctional mechanism is suggested for the heterodinuclear-complex-promoted cleavage of the phosphodiester bond. Double Lewis acid activation occurs when the metal ions bind to the phosphate oxygen atoms. In particular, a metal-bound hydroxide ion serves as a general base or a nucleophilic catalyst, and, presumably, a zinc(II)-bound aqua ligand behaves as a general acid and facilitates the departure of the leaving alkoxide group. The effect of the complexes on the hydrolysis of poly(U), poly(A) and type III native RNA was also investigated, and, for the first time, kinetic data on the cleavage of the phosphodiester bonds of polyribonucleotides by a dinuclear complex was obtained.
Chemistry 12/2003; 9(21):5404-15. · 5.93 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Five new dinuclear model complexes for zinc-containing phosphatases with dinucleating ligands have been prepared and characterized by single-crystal X-ray crystallography. The heterodinuclear, μ-alkoxo-bridged zinc(II)−iron(III) complexes 1−3 contain the symmetric ligands N,N,N′,N′-tetrakis[2-(5,6-dimethyl)benzimidazolylmethyl]-1,3-diamino-2propanol (Htdmbpo) and N,N,N′,N′-tetrakis{2-[N′′-(2hydroxyethyl)]benzimidazolylmethyl}-1,3-diamino-2-propanol (Hthebpo), and the asymmetric ligand N,N-bis[2-(4,5-dimethyl)benzimidazolylmethyl]-N′,N′-bis(2-pyridylmethyl)-1,3-diamino-2-propanol (Hbdmbbppo), respectively. X-ray crystallography revealed that the zinc center exhibits a trigonal-bipyramidal coordination, while the octahedral coordination sphere of the iron center is completed by a solvent molecule. In contrast, the zinc complexes 4 and 5, which also have (alkoxo)(cacodylato)dimetal cores with the dinucleating ligands used in 1 and 3, exhibit both metal centers in a trigonal-bipyramidal environment. Additionally, the solution speciation of the zinc(II) complexes formed with Htdmbpo and Hbdmbbppo were determined and the activity of the in situ prepared zinc complexes towards the transesterification of the RNA model substrate 2-(hydroxypropyl)-4-nitrophenyl phosphate (hpnp) was investigated. The dinuclear [Zn2LH−1(OH)]2+ complex of both ligands efficiently promotes the transesterification. The kinetic data indicated a higher activity for the complex of the asymmetric ligand Hbdmbbppo, as a result of its stronger substrate binding ability. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)
Berichte der deutschen chemischen Gesellschaft 04/2002; 2002(6):1400 - 1409. · 2.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The syntheses, crystal structures, solution equilibria and ribonuclease activity are reported for copper(II) and zinc(II) complexes of a new potentially dinucleating, bis-imidazole ligand N,N′-bis(5-methylimidazol-4-ylmethyl)-1,3-diaminopropan-2-ol (bimido). The zinc(II) ion in [Zn(bimido)Cl]NO3 is coordinated in a slightly distorted square pyramidal environment, with the four N atoms of bimido in the basal positions and the Cl− ion in the axial one. The two copper(II) ions in [Cu2(bimido−1H)(DPP)(ClO4)(CH3OH)]ClO4·1/2 H2O (DPP = diphenyl phosphate) are bridged by the deprotonated alkoxo group of bimido and by the phosphate group of DPP in a 1,3-bridging mode. Depending on the [M]/[L] ratio, the ML and M2L−2H species are present in solution in the neutral pH range, having analogous structures as described above for the crystalline complexes. The zinc(II)-bimido (2/1) system, in a 65% EtOH-H2O mixed solvent, shows an important increase of hydrolytic activity, parallel with the formation of the Zn2L−2H species, with a sigmoidal pH-rate profile modelling both steps of RNA hydrolysis. The kcat value for the transesterification of 2-hydroxypropyl-p-nitrophenyl phosphate by Zn2L−2H, determined from saturation kinetic measurements (T = 298 K), corresponds to a maximum rate acceleration (kcat/kuncat) of ca. 104. The observed pseudo-first order rate constant for the hydrolysis of uridine 2′,3′-cyclic monophosphate, under nearly physiological conditions (T = 310 K, pH = 8, [Zn2L−2H] = 3.6 mM, kobs = 2·10−5 s−1) reflects a higher hydrolytic activity of Zn2L−2H towards this biologically relevant substrate (kobs/kuncat indicates ca. 104 fold rate acceleration). The proposed mechanisms include bifunctional Lewis-acid and general base catalysis.
Berichte der deutschen chemischen Gesellschaft 07/2000; 2000(7):1635 - 1644. · 2.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Equilibrium (pH-metric) and spectroscopic (1H,13C, and 119Sn NMR and 119Sn Mössbauer) studies were performed to characterize the interaction of the dimethyltin(IV) cation with glycine, glycyl-glycine (Gly-Gly), imidazole-4-acetic acid, histamine, histidine, glycyl-histamine, glycyl-histidine (Gly-His), and β-alanyl-histidine (carnosine). For histamine and glycyl-histamine (having only nitrogen donor atoms) no complex formation was detected. The hydrolyzed species of the dimethyltin(IV) cation are always dominant over the complexes formed with the other ligands, except with Gly-Gly and Gly-His. For these two ligands, {COO-,N-,NH2} coordinated complexes are dominant in the neutral pH range with a trigonal bipyramidal structure, providing the first example that alkyltin(IV) cations are able to promote the deprotonation of the peptide-nitrogen in aqueous solutions, at unexpectedly low pH. In this process the carboxylate is the anchoring group (assisting by chelate formation), in contrast with any other metal ions which are known to coordinate to amide nitrogen. The metal coordination of the imidazole ring, which is suggested as binding site toward alkyltin(IV) cation in several proteins, was not observed for Gly-His under the conditions used; it is probably the case for the other ligands, too.
01/1999;
-
[show abstract]
[hide abstract]
ABSTRACT: The complex formation equilibria between pH 2 and 11.2 in Co(II)-L-O(2) ternary systems (L = histamine, glycylhistamine, and sarcosylhistamine) have been studied by pH-metric, spectrophotometric, and (1)H-NMR spectroscopic methods. In contrast to earlier findings, we detected several protonation states of oxygen-carrying complexes in the pH range 7-11.2. The active species in oxygen uptake is the CoL(2) complex already suggested in the Co(II)-histamine-O(2) system; however, in the case of pseudopeptides, both CoLH(-)(1) and CoL(2)H(-)(1) complexes can take up oxygen. The (1)H-NMR study revealed stereoisomerism of oxygenated species in the same protonation states, undergoing slow ligand exchange. In the case of the Co(2)(Hist)(4)(OH)(O(2)) complex, among the 20 possible geometrical isomers, at least six can be distinguished by their imidazole proton signals. The most abundant isomers have axial-equatorial imidazole coordination, presumably on steric grounds. The stability constants determined by pH studies for the above systems proved that {4N}-coordinated species have a greater affinity for oxygen uptake than the {3N}-coordinated ones. They also showed the stabilizing effect of the deprotonated amide nitrogen in the oxygenated complexes of pseudopeptides.
Inorganic Chemistry 05/1997; 36(9):1850-1859. · 4.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The macro- and microprotonations of glycylglycylhistamine (GGHA) have been determined by combined potentiometric and 1H-NMR methods. The complexation of GGHA with Co(II), Ni(II), and Cu(II) has been studied by potentiometric, EPR, and 1H-NMR methods. In the pH range 3−11.2, more or less deprotonated monomeric complexes (MLH, ML, MLH-1, MLH-2, MLH-3) formed in all systems. In the case of Ni(II) and Cu(II) at physiological pH, the MLH-2 species is predominant with four nitrogen coordination sites (one amino, two peptide, and one imidazole-N3 nitrogens) in square planar arrangement. In Co(II) containing systems however, CoL is the predominant complex near pH 7 with a macrochelate coordination of terminal amino and imidazole nitrogens, while CoLH-2 species forms at much higher pH. In accordance with NMR measurements, the formation of MLH-3 species can be assigned to the further deprotonation of the N1-pyrrolic nitrogen in the imidazole ring without metal coordination. The formation constants determined were compared with those of the analogous histidine derivatives. Single-crystal X-ray analysis of CuLH-2·3H2O verified the expected four nitrogen coordination in the equatorial plane of Cu(II).
01/1996;
-
[show abstract]
[hide abstract]
ABSTRACT: Equilibrium and spectroscopic (1H, 13C NMR and 119Sn Mössbauer) studies in aqueous solution are reported for dimethyltin(IV) complexes of 2-hydroxyhippuric acid (Sal-Gly). Below pH 4, oxygen-coordinated complexes MLH and ML are formed. In the pH range 5–8.5, the species MLH−1 predominates at any metal-to-ligand ratio. The ligand exchange of this species is slow on the NMR time scale, which allows its structural characterization by NMR spectroscopy: the coordination polyhedron around the tin atom is distorted trigonal bipyramidal, with tridentate {O−,N−,COO−} coordination of Sal-Gly, involving two equatorial methyl groups. The NMR results reveal that the main cause of the distortion of the polyhedron is the large CH3–Sn–CH3 angle of 136±4°. The presented results supplement the data available on the dimethyltin(IV)-promoted amide deprotonation of peptides, and provide further arguments for the fundamental role of the carboxylate as an anchoring group in this process.
Journal of Inorganic Biochemistry. 83:187-192.
