Macromolecular ionophores. 1. Chiral recognition properties of poly[(1→6)-2,5-anhydro-D-glucitol] toward racemic amino acid ester

The chiral recognition property of poly[(1→6)-2,5-anhydro-3,4-di-O-alkyl-D-glucitol] ( 1 ) toward racemic RCH (CO₂CH₃)NH₃⁺ · PF₆^? ( 2 · HPF₆) has been studied using a transport system involving an aqueous source and receiving phases separated by a chloroform phase containing 1 . Transport rates for aromatic guests 2a (R = Ph) and 2b (R = CH₂Ph) were faster than those for aliphatic guests, 2c (R = CH(CH₃)₂) and 2d (R = CH₂CH(CH₃)₂), using the polymer substituted with methyl groups ( 1a ). The enantiomeric excess (e.e.) was 10.9% for 2a as a maximum value and decreased in the order of 2a > 2c > 2b = 2d . When the transport of 2a · HPF₆ was carried out using the polymers with 3,4-di-O-methyl ( 1a ), ethyl ( 1b ), allyl ( 1c ), and pentyl ( 1d ) groups, the e.e. was 22.0% for 1d as a maximum value and increased in the order of 1a < 1b < 1c < 1d . The formation of a complex between 1a and 2a · HPF₆ was confirmed by ¹H and ¹³C NMR spectral measurements. © 1995 Wiley-Liss, Inc.     

Metal-penicillamine interactions. Part 1. Preparation and crystal structure of a 1:1 complex of mercuric chloride with d-penicillamine, 2[μ3-Cl){HgSC(CH3)2CH(NH3)COO}3·3(μ2-Cl)· 2(H3O)·(H2O·Cl)3

A 1:1 complex of mercuric chloride with D-peniccillamine has been isolated and characterised as 2[(μ₃-Cl){HgSC(CH₃)₂CH(NH₃)COO}3]·3(μ₂-Cl)·2(H₃O)·(H₂O·Cl)₃. The compound crystallises in cubic space group P4₁32, with a = 18.679(5) Å and Z = 4. The structure, refined to R_F = 0.086 for 443 observed Mo-Kα diffractometer data, features a triply bridging chloride ion linking three equivalent [HgSC(CH₃)₂CH(NH₃)COO]⁺ units [Hg-Cl = 2.37(1) Å, Hg-Cl-Hg′ = 98.5(9)°]. The carboxylate groups of a pair of adjacent penicillamine ligands are strongly linked via a symmetrical O?H?O hydrogen bond of length 2.24(8) Å, and neighboring pyramidal trinuclear [μ₃-Cl){HgSC(CH₃)₂CH(NH₃)-COO}₃]²⁺ moieties are further connected by symmetrical chloride bridges [Hg-Cl = 3.06(2) Å; HgClHg′' = 79.6(7)°] to form a three-dimensional network. The voids in the lattice are filled by hydronium ions and novel planar cyclic hydrogen-bonded (H₂O·Cl^?)₃ rings of edge O-H?Cl = 2.46(4) Å.     

Anticandidal cytotoxicity,antitumor activities,and purified cell wall modulation by novel Schiff base ligand and its metal (II) complexes against some pathogenic yeasts

The preparation of metal (II) complexes [CoCl₂·6H₂O, Ni(CH₃COO)₂·4H₂O, Cu(CH₃COO)₂·2H₂O, and Zn (CH3COO)₂ ·2H₂O] with 2[N-(cinnamlidene) amino]-5-nitro phenol as a novel ligands and their biological evaluation against candida species was studied. The inhibitory effects of the tested metal complexes were tested against six pathogenic yeasts (Candida albicans, C. fructus, C. glabrata, C. oleophila, C. parapsilosis, and C. tropicalis). The effect of the most efficient metal complex (Zn(II) complex) was more pronounced at 1.25 μg/ml, while Ni(II) complex was exhibited the least suppressive effect. Co(II) and Zn(II) complexes act as potential antitumor agents, while Zn(II) complex has shown promising cytotoxic activity with slow candidal respiration rate. Addition of Zn(II) complex leading to suppression of cell wall components in all candidal cells accompanied with leaking out of amino acids. Purification of the cell wall mannoprotein of C. glabrata treated with Zn(II) complex was established, resulting one pure fissured protein peak. Cell wall protein modulation was showed by appearance of two new protein bands with molecular weights of 72 and 39 KDa in C. glabrata cells treated with Zn(II) complex compared with one pure protein band 55.6 KDa in the non treated yeast cell.     

Effect of zinc on biological half-lives of 65Zn in whole body and liver and on distribution of 65Zn in different organs of rats following nickel toxicity

This study was designed to determine the effect of zinc on the biological half-lives of ⁶⁵Zn in whole body and liver and on distribution of ⁶⁵Zn in different organs of rats following nickel toxicity. Sprague-Dawley (SD) rats received either nickel in the form NiSO₄·6H₂O at a dose of 800 mg/L in drinking water, zinc in the form of ZnSO₄·7H₂O at a dose of 227 mg/L in drinking water, and nickel plus zinc or drinking water alone for a total duration of 8 wk. All of the rats were injected with a tracer dose of 0.37 MBq ⁶⁵Zn at the end of the treatment period. The effects of different treatments were studied on biological half-lives of ⁶⁵Zn in whole body and liver and on the distribution of ⁶⁵Zn in different organs of rats. In the present study, we have noted that nickel treatment to normal rats caused a significant decrease in the slow component (Tb₂) in liver, which improved following zinc supplementation. Nickel administration to normal-diet-fed animals caused significant lowering in the percentage uptake of ⁶⁵Zn values in the brain, liver, and intestine. However, the administration of zinc to nickel-treated rats improved the status of ⁶⁵Zn in different organs. The Tb₂ in the liver and the percentage uptake of ⁶⁵Zn values elevated following zinc supplementation to nickel-treated rats.     

Why the tautomerization of the G·C Watson–Crick base pair via the DPT does not cause point mutations during DNA replication? QM and QTAIM comprehensive analysis

The ground-state tautomerization of the G·C Watson–Crick base pair by the double proton transfer (DPT) was comprehensively studied in vacuo and in the continuum with a low dielectric constant (??=?4), corresponding to a hydrophobic interface of protein–nucleic acid interactions, using DFT and MP2 levels of quantum-mechanical (QM) theory and quantum theory “Atoms in molecules” (QTAIM). Based on the sweeps of the electron-topological, geometric, polar, and energetic parameters, which describe the course of the G·C???G^?·C^? tautomerization (mutagenic tautomers of the G and C bases are marked with an asterisk) through the DPT along the intrinsic reaction coordinate (IRC), it was proved that it is, strictly speaking, a concerted asynchronous process both at the DFT and MP2 levels of theory, in which protons move with a small time gap in vacuum, while this time delay noticeably increases in the continuum with ??=?4. It was demonstrated using the conductor-like polarizable continuum model (CPCM) that the continuum with ??=?4 does not qualitatively affect the course of the tautomerization reaction. The DPT in the G·C Watson–Crick base pair occurs without any intermediates both in vacuum and in the continuum with ??=?4 at the DFT/MP2 levels of theory. The nine key points along the IRC of the G·C base pair tautomerization, which could be considered as electron-topological “fingerprints” of a concerted asynchronous process of the tautomerization via the DPT, have been identified and fully characterized. These key points have been used to define the reactant, transition state, and product regions of the DPT reaction in the G·C base pair. Analysis of the energetic characteristics of the H-bonds allows us to arrive at a definite conclusion that the middle N1H?N3/N3H?N1 and the lower N2H?O2/N2H?O2 parallel H-bonds in the G·C/G^?·C^? base pairs, respectively, are anticooperative, that is, the strengthening of the middle H-bond is accompanied by the weakening of the lower H-bond. At that point, the upper N4H?O6 and O6H?N4 H-bonds in the G·C and G^?·C^? base pairs, respectively, remain constant at the changes of the middle and the lower H-bonds at the beginning and at the ending of the G·C???G^?·C^? tautomerization. Aiming to answer the question posed in the title of the article, we established that the G^?·C^? Löwdin’s base pair satisfies all the requirements necessary to cause point mutations in DNA except its lifetime, which is much less than the period of time required for the replication machinery to forcibly dissociate a base pair into the monomers (several ns) during DNA replication. So, from the physicochemical point of view, the G^?·C^? Löwdin’s base pair cannot be considered as a source of point mutations arising during DNA replication.     

The use of hydrogenated Schiff base ligands in the synthesis of multi-metallic compounds

The synthetic utility of tris-((2-hydroxybenzyl)-aminoethyl)amine (H6TrenSal) and tris-((2-hydroxy-5-bromobenzyl)-aminoethyl)amine (H6Tren5BrSal) are investigated. A range of monomeric complexes with general formula [(H6TrenSal)M][NO₃] with nickel, copper and zinc are reported and crystallographically analysed. Nickel adopts three motifs which are different to that observed for copper and zinc. The use of these species as platforms for the synthesis of more complex systems in conjunction with the lanthanoids are explored. Copper and zinc do not follow a similar reaction pathway to nickel. While nickel forms the expected trimetallic motif [{(TrenSal)Ni}₂Ln(HOMe)]⁺, copper forms a copper trimetallic motif. In contrast to both nickel and copper, reactions with [(H6TrenSal)Zn]⁺ produce lanthanoid based products namely [(H6Tren5BrSal)Gd(NO₃)₃] and [{(H6TrenSal)Ce}₂-μ²-O₂].     

Studies on interaction between poly(L-lysine) and DNA of varied G + C contents

Interaction between polylysine and DNA's of varied G + C contents was studied using thermal denaturation and circular dichroism (CD). For each complex there is one melting band at a lower temperature t_m, corresponding to the helix–coil transition of free base pairs, and another band at a higher temperature t′_m, corresponding to the transition of polylysine-bound base pairs. For free base pairs, with natural DNA's and poly(dA-dT) a linear relation is observed between the t_m and the G + C content of the particular DNA used. This is not true with poly(dG)·poly(dC), which has a t_m about 20°C lower than the extrapolated value for DNA of 100% G + C. For polylysine-bound base pairs, a linear relation is also observed between the t′_m and the G + C content of natural DNA's but neither poly(dA-dT) nor poly(dG)·poly(dC) complexes follow this relationship. The dependence of melting temperature on composition, expressed as dt_m/dX_G·C, where X_G·C is the fraction of G·C pairs, is 60°C for free base pairs and only 21°C for polylysine-bound base pairs. This reduction in compositional dependence of T_m is similar to that observed for pure DNA in high ionic strength. Although the t′_m of polylysine-poly(dA-dT) is 9°C lower than the extrapolated value for 0% G + C in EDTA buffer, it is independent of ionic strength in the medium and is equal to the t_m⁰ extrapolated from the linear plot of t_m against log Na⁺. There is also a noticeable similarity in the CD spectra of polylysine· and polyarginine·DNA complexes, except for complexes with poly(dA-dT). The calculated CD spectrum of polylysine-bound poly(dA-dT) is substantially different from that of polyarginine-bound poly(dA-dT).     

Interactions of DNA with divalent metal ions. IV. Competitive studies of Mn2+ binding to AT- and GC-rich DNAs

It has been inferred from previous studies that Mn²⁺ ions bind preferentially to G·C base pairs in DNA, and it has even been suggested that this preference for G·C pairs might be responsible for some of the Mn²⁺ specific effects observed in various biochemical reactions. In this paper we investigate the AT/GC preference of Mn²⁺ by direct competition studies in which AT-rich DNA was dialyzed against GC-rich DNA in the presence of varying amounts of Mn²⁺. Analysis of these results demonstrates that over a wide range of Mn²⁺/DNA(P) molar ratios, Mn²⁺ binds to A·T and to G·C base pairs with virtually identical affinity, although in a somewhat different mode. Both the present and previous nmr, uv, CD, and melting studies are discussed in terms of the different modes of binding of Mn²⁺ to single- and double-stranded DNA.     

The formation constants of dimethylthallium(III)-glutathione complexes in aqueous solution

The complexes formed in the dimethylthallium(III) (Me₂Tl⁺), glutathionate (EGC³⁻) and hydrogen ion system in aqueous solution at 37 °C and I = 150 mmol dm⁻³ (NaCl) have been characterised by means of glass-electrode potentiometry. Glutathione protonation constants were found to be 9.123 ± 0.007, 17.42 ± 0.01, 20.78 ± 0.02, and 22.93 ± 0.02. Formation constants for the complexes [(Me₂Tl)EGCH]⁻ and [(·Me₂Tl) EGC]²⁻ were found to be 11.19 ± 0.03 and 2.39 ± 0.02, respectively. Particular attention has been paid to the evaluation of the effect of possible systematic errors on the constant values determined. Reliable standard deviation estimations have been made by applying a Monte Carlo calculation technique.     

The nature of the transition mismatches with Watson–Crick architecture: the G*·T or G·T* DNA base mispair or both? A QM/QTAIM perspective for the biological problem

This study provides the first accurate investigation of the tautomerization of the biologically important guanine*·thymine (G*·T) DNA base mispair with Watson–Crick geometry, involving the enol mutagenic tautomer of the G and the keto tautomer of the T, into the G·T* mispair (?G?=?.99?kcal?mol^?1, population?=?15.8% obtained at the MP2 level of quantum-mechanical theory in the continuum with ε?=?4), formed by the keto tautomer of the G and the enol mutagenic tautomer of the T base, using DFT and MP2 methods in vacuum and in the weakly polar medium (ε?=?4), characteristic for the hydrophobic interfaces of specific protein–nucleic acid interactions. We were first able to show that the G*·T?G·T* tautomerization occurs through the asynchronous concerted double proton transfer along two antiparallel O6H···O4 and N1···HN3 H-bonds and is assisted by the third N2H···O2 H-bond, that exists along the entire reaction pathway. The obtained results indicate that the G·T* base mispair is stable from the thermodynamic point of view complex, while it is dynamically unstable structure in vacuum and dynamically stable structure in the continuum with ε?=?4 with lifetime of 6.4·10^?12?s, that, on the one side, makes it possible to develop all six low-frequency intermolecular vibrations, but, on the other side, it is by three orders less than the time (several ns) required for the replication machinery to forcibly dissociate a base pair into the monomers during DNA replication. One of the more significant findings to emerge from this study is that the short-lived G·T* base mispair, which electronic interaction energy between the bases (?23.76?kcal?mol^?1) exceeds the analogical value for the G·C Watson–Crick nucleobase pair (?20.38?kcal?mol^?1), “escapes from the hands” of the DNA replication machinery by fast transforming into the G*·T mismatch playing an indirect role of its supplier during the DNA replication. So, exactly the G*·T mismatch was established to play the crucial role in the spontaneous point mutagenesis.     

Crystal structure of zinc citrate

The crystal structure of zinc citrate [Zn(II) (C₆H₅O₇)₂·4NH₄⁺] shows isolated zinc ions octahedrally coordinated to two equivalent citrates via a central hydroxyl, central carboxyl, and one terminal carboxyl from each citrate. The clusters are linked through hydrogen bonds to ammonium ions in the lattice. The structure is distinctly different from that of other divalent cation triply ionized citrate complexes, which are polymeric. Crystal data : space group P2₁/C, a = 8.784(3) Å, b = 13.499(4) Å, c = 9.083(3) Å, β = 113.4°(1), V = 988(1) ų. Citrate has been identified as the low molecular weight ligand that complexes zinc in human milk; this may be of interest in relation to intestinal zinc absorption.     

Synthesis and characterization of thiolato-bridged cadmium(II) complexes with NNS-chelating thiolic ligands

Cadmium(II) complexes with 2-[(2-aminoethyl)amino]ethanethiol (HL¹), 2-[(3-aminopropyl)amino]ethanethiol (HL²), 2-[(2-pyridylmethyl)amino]ethanethiol (HL³), and 2-[[2-(2-pyridyl)ethyl]amino]ethanethiol (HL⁴), [Cd(L¹)](ClO₄) (1), [Cd(L²)](ClO₄)·1/2CH₃OH (2), [Cd{Cd(L²)₂}₂](ClO₄)₂·CH₃CON(CH₃)₂ (3a·CH₃CON(CH₃)₂), [Cd{Cd(L²)₂}₂]Cl₂·2CH₃OH (3b·2CH₃OH), [Cd{Cd(L³)₂}₂](ClO₄)₂ (4), [Cd(L⁴)](ClO₄) (5), have been synthesized and characterized by measurements of the infrared and electronic spectra. The X-ray crystal structures show that 3a and 3b have a thiolato-bridged trinuclear core with a linear arrangement of three metal atoms.     

Evidence for long-range interactions in DNA. Analysis of melting curves of block polymers d(C15A15)·d(T15G15), d(C20A15)·d(T15G20), and d(C20A10)·d(T10G20)

The influence of one DNA region on the stability of an adjoining region (telestability) was examined. Melting curves of three block DNA's, d(C₁₅A₁₅)·d(T₁₅G₁₅), d(C₂₀A₁₅)·d(T₁₅G₂₀), and d(C₂₀A₁₀)·d(T₁₀G₂₀) were analyzed in terms of the nearest neighbor Ising model. Comparisons of predicted and experimental curves were made in 0.01 M and 0.1 M sodium ion solutions. The nearest neighbor formalism was also employed to analyze block DNA transition in the presence of actinomycin, a G·C specific molecule. The results show that nearest neighbor base-pair interaction cannot predict the melting curves of the block DNA's. Adjustments in theoretical parameters to account for phosphate repulsion assuming a B conformation throughout the DNA's do not alter this conclusion. Changes in the theoretical parameters, which provide good overall agreement, are consistent with a substantial stabilization of the A·T region nearest the G·C block. The melting temperature T A·T for the average A·T pari in d(C₂₀A₁₀)·d(T₁₀G₂₀), with 10 A·T pairs, appears to be 4°C greater than T_A·T for d(C₁₅A₁₅)·d(T₁₅G₁₅) and d(C₂₀A₁₅)·d(T₁₅G₂₀), both with 15 A·T pairs. Actinomycin bound to the G·C end effectively stabilizes the A·T end by 9°C. These results indicate a long-range contribution to the interactions governing DNA stability. A possible mechanism for these interactions will be discussed.     

Correlation of Tm and sequence of DNA duplexes with delta H computed by an improved empirical potential method

T_m values for 20 DNA duplexes with different repeating base sequences provided the data base for developing a rational and relatively simple methodology for computing apparent enthalpies for the helix → coil transitions of DNA helices, ΔH _calc. The computational variables and their range of acceptable values were selected on the basis of physically plausible arguments. Over 350,000 different combinations of the variables were tested for degree of fit. It was therby possible to find a combination giving a high degree of linear fit between T_m and ΔH _calc (correlation coefficient, 0.99), with T_m values deviating (on average) from the regression line by only ±2.17°C. Most of this uncertainty is attributed to experimental limitations, although computational approximations also contribute. With ΔH _calc for the melting of each of the unique complementary dinucleotide fragments computed by the method developed, it is possible to estimate T_m and (relative) ΔH _calc reliable for the melting of any particular DNA [with base pairs G(I)·C and A·T] given only its base sequence. The ΔH_calc values for the complementary dinucleotide fragments, together with statistical considerations, make it apparent that T_m of DNAs with repeating base sequence show only an approximate linear dependence on G·C content because A·T and G·G pairs do not contribute to helix stability independently of the base-pair sequence in which they occur. In fact, the nearestneighbor stacking interactions are so significant that certain complementary dinucleotide fragment sequences with 0,50, and 100% G·C content have the same stability.     

Syntheses and characterization of neutral complexes of Zn(II) with mono- and dianionic pyrrole-2-imine ligands [(pyrrole-2-CHN)nR]n− (n = 1, 2)

The reactions of the dianionic [(pyrrole-2-CHN)₂R]^2? ligands [(N′₂N₂)^2?] (R = (R)(S)-1,2-cyclohexane or 1,2-ethane) with Zn(II) yield neutral dimeric [Zn₂(N′₂N₂)₂] complexes. The dimeric nature of the complexes was established by field-desorption mass spectrometry. ¹H NMR studies show that these complexes have dimeric structures in solution in which the (N′₂N₂)^2? ligands act as di-bidentates.The metal centres have tetrahedral geometries and bot have Δ or Λ configurations. The complex with the (R)(S)-1,2-cyclohexanediyl bridges has a rigid structure in solution. Neither intermolecular nor intramolecular exchange processes are observed The ¹H NMR spectrum of the complex with the 1,2-ethanediyl bridging groups shows that at 213 K in CDCl₃ a fast conformational movement is already taking place between two identical structures of the complex. It is not possible to determine whether in this complex intermolecular exchange processes are also taking place.The reactions of the anionic [pyrrole-2-CHNR′]^? ligands [(N′N)^?] (R′ = t-Bu, i-Pr, (S)-CHMePh or 2,6-xylyl) with Zn(II) yield the neutral Zn(N′N)₂ complexes. These complexes were synthesized to study the coordination properties of the [pyrrole-2-CHNR′]^? moieties with Zn(II). A ¹H NMR study established that the zinc centres in the complexes containing the prochiral i-Pr or chiral (S)-CHMePh substituents have tetrahedral geometries with Δ or Λ configurations in CDCl₃ at 213 K. These complexes undergo an intramolecular exchange process at higher temperatures (above 260 K when R′ = i-Pr) which involves inversion of the configuration of the zinc centre. A mechanism for this exchange process is proposed.     

Parallel-Stranded Oligonucleotides with Alternating d(A-isoG)/d(T·C) and d(A·G)/d(T·m5isoC) Sequences

Abstract

Parallel-stranded (ps) DNA hairpins with alternating d(A-isoG)/d(T·C) (designated as ps-t1) and d(A·G)/d(T·m⁵isoC) (ps-t2) sequences were studied by means of UV, CD and fluorescence spectroscopy. The thermostability of d(A·G)/d(T·m⁵isoC) sequence was close to that of aps d(G·A)/d(T·C). The stability of the ps d(A·isoG)/d(T·C) sequence was even higher than that of a related anti-parallel-stranded (aps) d(G·A)/d(T·C) sequence, being unique for ps DNAs studied so far.     

S versus O alkylation and coordination in zinc complexes containing the bulky heteroscorpionate alkoxy ligand bis(3,5-dimethylpyrazol-2-yl) diphenylmethanol

A series of zinc complexes containing the tripodal heteroscorpionate ligand bis(3,5-dimethylpyrazol-2-yl)diphenylmethanol (L2H) have been synthesized and characterized by X-ray crystallography. The L2H/Zn complexes were designed to model the N₂OX coordination (with the zinc-bound O being a reactive nucleophile) that is characteristic of many protease and amidase zinc enzymes. The pseudotetrahedral mononuclear complexes characterized include [(L2)ZnI] (1), [(L2)Zn(CH₃)] (2), and [(L2)Zn(SPh)] (3). Alkylation of (1) with methyl iodide has revealed a modest nucleophilicity of the chelated zinc-bound alkoxide, and produces the penta-coordinate [(L2OCH₃)ZnI₂] (4) which contains a weakly bound ether in the fifth coordination site. However, when the coordination sphere also includes a thiolate sulfur as in (3), reaction with methyl iodide produces exclusive alkylation at the sulfur to produce thioanisole and (1). The coordination of the ether in the neutral (4) can be strengthened by reaction with various silver salts, Ag⁺X⁻, to produce other penta-coordinate complexes [(L2OCH₃)ZnI(Tf)] (5) and [(L2OCH₃)ZnI(H₂O)]BF₄ (6) which show enhanced coordination of the ether.