Mixed-Ligand Complexes of 2-(Aminomethyl)benzimidazole Palladium(II) with Various Biologically Relevant Ligands

cis-Dichloro(2-(aminomethyl)benzimidazole)palladium(II), [Pd(AMBI)Cl₂], was synthesized and characterized. The stoichiometry and stability constants of the complexes formed between [Pd(AMBI)(H₂O)₂]²⁺ with various biologically relevant ligands containing different functional groups are investigated. The ligands used are dicarboxylic acids, amino acids, peptides and DNA constitutents. The results show the formation of 1:1 complexes with amino acids and dicarboxylic acids. The effect of the chelate ring size of the dicarboxylic acid complexes on their stability constants is examined. Peptides form both 1:1 complexes and the corresponding deprotonated amide species. Structural effects of the peptide on the amide deprotonation are investigated. DNA pyrimidinic constituents such as uracil, uridine, thymidine and thymine form 1:1 and 1:2 complexes, whereas purinic constituents such as inosine 5′-monophosphate (5′-IMP) and guanosine 5′-monophosphate (5′-GMP) form only 1:1 complexes. The concentration distribution of the complexes in solution was evaluated. The effect of increasing chloride ion concentration on the formation constant of CBDCA with Pd(AMBI)²⁺ was reported.     

Potentiometric and Speciation Studies on the Complex Formation Reactions of [Pd(2-methylaminomethyl)-pyridine)(H<Subscript>2</Subscript>O)<Subscript>2</Subscript>]<Superscript>2+</Superscript> with Some Bio-active Ligands and Displacement Reaction of Coordinated Inosine

The stoichiometry and stability constants of the complexes formed between [Pd(MAMP)(H₂O)₂]²⁺ and various biologically relevant ligands containing different functional groups were investigated. The ligands used are amino acids, peptides and DNA constituents. The results show the formation of 1:1 complexes with amino acids and peptides and the corresponding deprotonated amide species. Structural effects of peptides on amide deprotonation were investigated. The purine and pyrimidine bases uracil, uridine, cytosine, inosine, inosine 5′-monophosphate (5′-IMP) and thymine form 1:1 and 1:2 complexes. The concentration distribution of the various complex species was calculated as a function of pH. The effect of chloride ion concentration on the formation constant of CBDCA with Pd(MAMP)²⁺ was also reported. The results show ring opening of CBDCA and monodentate complexation of the DNA constituent with the formation of [Pd(MAMP)(CBDCA-O)DNA], where (CBDCA-O) represents cyclobutane dicarboxylate coordinated by one carboxylate oxygen. The equilibrium constant of the displacement reaction of coordinated inosine, as a typical DNA constituent, by SMC and/or methionine was calculated. The results are expected to contribute to the chemistry of antitumor agents. The calculated parameters of the optimized complexes support the measured formation constants.     

Mixed ligand complexes of [Pd(terpy)(H2O)]2+ with some selected amino acids,peptides, DNA and related ligands

Stability constants of the ternary palladium(II) complexes of triamine 2,2′:6′,2″-terpyridine (terpy) and some amino acids, peptides, DNA constituents or thiols were determined at 25 °C and at constant 0.1 mol dm⁻³ ionic strength, adjusted using NaNO₃. The coordination sites are pH-dependent. The results show the formation of binuclear species, 210. The speciation diagrams of various complex species were evaluated as a function of pH. Good correlations were found between the stability constants of the complexes and basicity of ligands.     

Tripropyltin(iv) complexes with some selected bioligands in 50% v/v dioxane/water mixture

The interaction of the tri-n-propyltin(IV) (TPT) with some selected bioligands having a variety of model functional groups were investigated using potentiometric technique at 25 degrees C and 0.1 M ionic strength in 50% v/v dioxane/water mixture. TPT is hydrolyzed to give [(C3H7)3SnOH], [(C3H7)3Sn(OH)2]-, and [((C3H7)3Sn)2OH]+. Amino acids and DNA constituents form 1:1 and 1:2 complexes. Peptides form 1:1 complexes and the corresponding deprotonated amide species. The protonated complexes are formed with amino acids, peptides and some DNA constituents. The hydrolysis constants and the stepwise formation constants of the complexes formed in solution were calculated using the nonlinear least-square program MINIQUAD-75. The participation of different ligand functional groups in binding to organotin is discussed. The speciation diagrams of the various complex species were evaluated as a function of pH.     

Equilibrium studies of complex formation involving palladium(II)-(1,3-diaminopropane) and cyclobutane dicarboxylic acid,DNA units,amino acids or peptides

Complex formation equillibria of [Pd(DAP)(H₂O)₂]²⁺ (DAP = 1,3-diaminopropane) with Cl⁻, OH⁻, cyclobutane dicarboxylic acid (CBDCA), amino acids, peptides and DNA unit constituents have been investigated. Stoichiometries and stability constants of the complexes were determined at 37°C and 0.16 M NaNO₃ ionic strength. The results showed the formation of 1:1 complexes with amino acids and CBDCA. Peptides form both 1:1 complexes and the corresponding deprotonated amide species. DNA constituents form both 1:1 and 1:2 complexes. [Pd(DAP)(CBDCA)] was isolated and characterized. The concentration distribution of the complexes in solution was evaluated. This revised version was published online in June 2006 with corrections to the Cover Date.     

INVESTIGATION OF THE SOLUTION STRUCTURE OF Cu(II) MIXED-LIGAND COMPLEXES OF ADENOSINE 5′-MONOPHOSPHATE AND CYTIDINE 5′-MONOPHOSPHATE AND POLYAMINES

Abstract

The coordination mode of complexes formed in the systems Cu(II)/NMP/PA; (NMP =adenosine 5′-monophosphate, cytidine 5′-monophosphate; PA = 1,4-diaminopropane (putrescine, Put), 1,7-diamino-4-azaheptane (3,3-tri) and 1,11-diamino-4,8-diazaundekane (3,3,3-tet)) was determined on the basis of the equilibrium and spectroscopic studies. The presence of the following mixed complexes was established: Cu(CMP)H(Put), Cu(AMP)H₂(3,3-tri) and Cu(CMP)H₂(3,3-tri), Cu(CMP)H₄(3,3-tri) and coordination compounds of MLL′ type-Cu(CMP)(3,3,3-tet), Cu(AMP)(3,3,3-tet). A significant influence of the polyamine length on the solution structure of the complexes was observed. In mixed-ligand complexes Cu(NMP)(3,3,3-tet) a {N4, O} chromophore is formed, and metallation involves all nitrogen atoms from 3,3,3-tet. In the analogous system with 3,3-tri, protonated complexes occur. Non-covalent intramolecular interaction between the protonated amine groups and donor atoms from the purine ring from the nucleotide results in an increase of complex stability.     

Potentiometry, Stability and Thermodynamics of Diethyltin(IV) Dichloride with Some Selected Biomolecules

The interaction of diethyltin(IV), DET, with selected bioligands having a variety of model functional groups was investigated at 25 °C and ionic strength 0.1 mol·dm^?3 NaCl using the potentiometric technique. The hydrolysis constants of the DET cation and the formation constants of the complexes formed in solution were calculated using the MINIQUAD-75 program. The stoichiometry and stability constants for the complexes formed are reported. The results show the formation of 1:1 and 1:2 complexes with amino acids and DNA constituents. The dicarboxylic acids form 1:1 complexes. The peptides form both 110 complexes and the corresponding deprotonated amide species [Et₂Sn(LH_?1)] (11-1). The participation of different ligand functional groups in binding to organotin is discussed. The concentration distributions of the various complex species were evaluated as a function of pH. The standard thermodynamic parameters ΔH° and ΔS°, calculated from the temperature dependence of the equilibrium constants, were investigated for the interaction of DET with thymine as a representative example of DNA constituents. The effect of ionic strength and solvent on hydrolysis constants of DET, protonation equilibria of thymine and its complex formation with DET were investigated and discussed.     

Binary and Ternary Complexes of Copper(II) Involving N,N,N′,N′-Tetramethylethylenediamine (Me4en) and Various Biologically Relevant Ligands

Binary and ternary complexes of copper(II) involving N,N,N′,N′-tetramethylethylene-diamine (Me₄en) and various biologically relevant ligands containing different functional groups are investigated. The ligands (L) used are dicarboxylic acids, amino acids, peptides and DNA unit constituents. The ternary complexes of amino acids, dicarboxylic acids or peptides are formed by simultaneous reactions. The results showed the formation of Cu(Me₄en)(L) complexes with amino acids and dicarboxylic acids. The effect of chelate ring size of the dicarboxylic acid complexes on their stability constants was examined. Peptides form both Cu(Me₄en)(L) complexes and the corresponding deprotonated amide species Cu(Me₄en)(LH₋₁). The ternary complexes of copper(II) with (Me₄en) and DNA are formed in a stepwise process, whereby binding of copper(II) to (Me₄en) is followed by ligation of the DNA components. DNA constituents form both 1:1 and 1:2 complexes with Cu(Me₄en)²⁺. The concentration distribution of the complexes in solution was evaluated. [Cu(Me₄en)(CBDCA)] and [Cu(Me₄en)(malonate)] are isolated and characterized by elemental analysis and infrared measurements.     

Complex Formation Reactions of Divinyltin(IV) Complexes with Amino Acids,Peptides, Dicarboxylic acids and Related Compounds

Complex formation equilibria of divinyltin(IV) with amino acids, peptides, and dicarboxylic acids have been investigated. Stoichiometry and stability constants for the complexes formed were determined at 25°C and ionic strength 0.1 M NaNO₃. The results showed the formation of ML, MLH, and ML₂ (organotin : ligand : hydrogen) complexes with amino acids. Peptides form ML complexes and the corresponding deprotonated amide species MLH_?1. In the latter species the binding with divinyltin(IV) occurs through the terminal amino group, carboxylate oxygen, and the amide nitrogen atoms (CO^? ₂, N^? _amide, NH₂). The results showed the formation of ML and ML₂ complexes with dicarboxylic acids. The concentration distribution of the complexes in solution was evaluated. The bonding sites of the divinyltin(IV) complex in solid state with oxalic acid was investigated by means of elemental analyses, FTIR, and mass spectra. Non-isothermal decomposition of the above complex has been studied and the result was statistically analyzed. The main steps were identified for the thermal decomposition reaction and each step proved to be a first order reaction. The kinetic parameters E _a and A were calculated for each step in the reaction. The thermodynamic functions H, G, and S* were calculated for each step of the reaction.     

Complex formation reactions of palladium(II)-1,3-diaminopropane with various biologically relevant ligands. Kinetics of hydrolysis of glycine methyl ester through complex formation

The interaction of [Pd(DAP)(H₂O)₂]²⁺ (DAP = 1,3-diaminopropane) with some selected bio-relevant ligands, containing different functional groups, were investigated. The ligands used are dicarboxylic acids, amino acids, peptides and DNA constituents. Stoichiometry and stability constants of the complexes formed are reported at 25°C and 0.1 M ionic strength. The results show the formation of 1:1 complexes with amino acids and dicarboxylic acids. The effect of chelate ring size of the dicarboxylic acid complexes on their stability constants is examined. Peptides form both 1:1 complexes and the corresponding deprotonated amide species. DNA constituents form 1:1 and 1:2 complexes. The effect of dioxane on the acid dissociation constants of CBDCA and the formation constant of its complex with Pd(DAP)²⁺ was reported. The kinetics of hydrolysis of glycine methyl ester bound to [Pd(DAP)(H₂O)₂]²⁺ was studied at 25°C and 0.1M ionic strength.      

Transfer ribonucleic acids

Transfer ribonucleic acids (tRNAs)

1 Abbreviations used according to IUPAC-IUB convention: tRNA = transfer ribonucleic acid; tRNA_yeast = mixture of tRNAs from yeast; tRNA^Phe = phenylalanine specific tRNA; Phe-tRNA = tRNA esterified (“charged”) with Phe; mRNA = messenger RNA; DNA = deoxyribonucleic acid; U = uridine; A = adenosine; C = cytidine; G = guanosine; pA = 5′-adenylic acid; Ap or A- = 3′-adenylic acid; m²′G = 2′-O-methyl guanosine; m⁷G = 7-methyl guanosine; mG = N(2)-dimethyl guanosine; other methylated nucleosides are abbreviated analogously; abbreviations of other odd nucleosides are given with Fig. 2; p or – signifies phosphate; RNase = ribonuclease; DEAE = diethylaminoethyl; fMet = N-formayl methionine.

occur in all living organisms. In biological protein synthesis they accept activated amino acids which are then transferred to growing peptide chains. With molecular weights lying between 25000 and 30000, tRNAs are easily within the reach of today's physical, chemical, and biochemical methods. The primary structures of several tRNAs as well as some relationships between structure and function have been elucidated. Three-dimensional structure, specificity, and mechanism of action are the subjects of present research efforts.     

Ternary Complexes of La(III), Ce(III), Pr(III) or Er(III) with Adenosine 5′-mono, 5′-di,and 5′-triphosphate as Primary Ligands and some Biologically Important Zwitterionic Buffers as Secondary Ligands

Equilibrium constant measurements have been performed potentiometrically at (25±0.1) °C and an ionic strength I=0.1 mol⋅dm⁻³ KNO₃ for the interaction of La(III), Ce(III), Pr(III) and Er(III) with the purine nucleotides adenosine 5′-mono, 5′-di, and 5′-triphosphate and with the biologically relevant secondary ligand zwitterionic buffers 3-(cyclohexyl amino)-1-propanesulfonic acid (CAPS), 3-(cyclohexylamino)-2-hydroxy-1-propane sulfonic acid (CAPSO), N-tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid (TAPS), 3-[N-bis(hydroxyethyl)amino]-2-hydroxypropanesulfonic acid (DIPSO), N,N-bis(2-hydroxyethyl)glycine (BICINE), and N-(2-acetamido)-2-iminodiacetic acid (ADA) in a 1:1:1 ratio. The formation of various 1:1:1 normal and protonated mixed-ligand complex species was inferred from the potentiometric pH titration curves. The experimental conditions were selected such that self-association of the purine nucleotides and their complexes was negligibly small; that is, the monomeric normal and protonated ternary complexes were studied. Initial estimates of the formation constants of the resulting species and the acid dissociation constants of adenosine 5′-mono-, 5′-di-, and 5′-triphosphate and the zwitterionic buffer secondary ligands were refined with the Superquade computer program. In some Ln(III) mixed-ligand systems, interligand interactions between the coordinating ligands, possibly involving H-bond formation, have been found to be the most important factors in deciding the stability of the mixed-ligand complexes in solutions. The thermodynamic ΔG° values of the monomeric normal and protonated ternary complexes were calculated and discussed.     

Absorption spectra of chelates of nitrosonaptholsulphonic acids with vanadaium(IV)

The absorption spectra of chelates formed by oxovanadium(IV) with five different o-nitro-sonaphtholsulphonic acids in aqueous solution are presented. All the ligands studied, 1-nitroso-2-naphthol-3,6-disulphonate (Nitroso-R salt), 2-nitroso-1-naphthol-4-sulphonate, 2-nitroso-1-naphthol-5-sulphonate, 2-nitroso-1-naphthol-8-sulphonate and 2-nitroso-1-naphthol-4,6-disulphonate, form red-brown vanadium(IV) chelates in acid solution. Values of the first Stability constants of the complexes are reported.     

Noncovalent Interaction of Uridine 5′-Monophosphate with Adenosine, Cytidine, and Thymidine, as well as Adenosine 5′-Monophosphate and Cytidine 5′-Monophosphate in Aqueous Solution

Adduct formation has been studied in the systems of uridine 5′-monophosphate (UMP) with adenosine (Ado), cytidine (Cyd), thymidine (Thd), adenosine 5′-monophosphate (AMP), and cytidine 5′-monophosphate (CMP) by the potentiometric method with computer analysis of the data and ¹³C and ³¹P NMR spectroscopic measurements. It has been established that in the complexes identified, ion–dipole and dipole–dipole interactions occur with the positive reaction centers being protonated nitrogen atoms N(3) of UMP or Thd, and at low pH values, endocyclic nitrogen atoms of the other nucleosides and nucleotides, as e.g., in (UMP)H₂(Ado). The negative reaction centers are the high-electron density atoms N(1) and N(7) from Ado or AMP and N(3) from Cyd or CMP, and the phosphate group of the nucleotides studied, which already undergo partial deprotonation at low pH values. The NMR results have established the presence of noncovalent stacking-type interactions in certain molecular complexes, e.g., (UMP)H₂(AMP). The sites of ion–dipole or dipole–dipole interactions are generated as a result of deprotonation of the nucleosides and nucleotides in the pH range of formation of molecular complexes. Analysis of the equilibrium constants of the reaction allowed a determination of the effectiveness of the phosphate groups and donor atoms of heterocyclic rings in the process of molecular complex formation.     

The determination of the stability constants of mixed ligand complexes of adenine and amino acids with Ni(II) by potentiometric titration method

A potentiometric titration technique has been used to determine the stability constants for the various complexes of Ni(II) with adenine (A) as primary ligand and selected amino acids (L) as secondary ligands. Ternary complexes of amino acids are formed in a stepwise mechanism, whereby (A) binds to Ni(II), followed by interaction with ligand (L), whereas thiol-containing ligands form ternary complexes through a simultaneous mechanism. The formation constants of the complexes were determined at 25 °C and ionic strength 0.1 M NaNO₃. The relative stabilities of the ternary complexes are compared with those of the corresponding binary complexes in terms of Δlog K values. The concentration distribution of the complexes are evaluated.     

Complex Formation Reactions of Promethazine Copper(II) and Various Biologically Relevant Ligands. Synthesis,Equilibrium Constants,Spectroscopic Characterization and Biological Activity

Binary and ternary complexes of copper(II) involving promethazine, N,N-dimethyl-3-(phenothiazin-10-yl)propylamine (Prom) and various biologically relevant ligands containing different functional groups, were investigated. The ligands (L) are dicarboxylic acids, amino acids, amides and DNA constituents. The ternary complexes of amino acids, dicarboxylic acids or amides are formed by simultaneous reactions. The results showed the formation of Cu(Prom)(L) complexes with amino acids and dicarboxylic acids. The effect of chelate ring size of the dicarboxylic acid complexes on their stability constants was examined. Amides form both Cu(Prom)(L) complexes and the corresponding deprotonated species Cu(Prom)(LH₋₁). The ternary complexes of copper(II) with (Prom) and DNA are formed in a stepwise process, whereby binding of copper(II) to (Prom) is followed by ligation of the DNA components. DNA constituents form both 1:1 and 1:2 complexes with Cu(Prom)²⁺. The stability of these ternary complexes was quantitatively compared with their corresponding binary complexes in terms of the parameters Δlog₁₀ K. The values of Δlog₁₀ K indicate that the ternary complexes containing aromatic amino acids were significantly more stable than the complexes containing alkyl- and hydroxyalkyl-substituted amino acids. The concentration distribution of various complex species formed in solution was also evaluated as a function of pH. The solid complexes [Cu(Prom)L)] where L=1,1-cyclobutanedicarboxylic acid (CBDCA), oxalic and malonic acid were isolated and characterized by elemental analysis, infrared, TGA, and magnetic susceptibility measurements. Spectroscopic studies of the complexes revealed that the complexes exhibits square planar coordination with copper(II). The isolated solid complexes have been screened for their antimicrobial activities using the disc diffusion method against some selected bacteria and fungi. The activity data show that the metal complexes are found to have antibacterial and antifungal activity.     

Adsorption of amino acids on a cerium dioxide surface

Adsorption of glutamic, aspartic, and pteroylglutamic (folic) acids from aqueous solutions on the surface of nanocrystalline cerium dioxide has been studied as depending on the pH and ionic strength of the solutions. Stability constants have been calculated for surface complexes that result from the interaction of anionic forms of the amino acids with protonated surface groups of cerium dioxide. The structure of the surface complexes has been confirmed by IR spectroscopy.     

Investigation of the interactions between ginsenosides and amino acids by mass spectrometry and theoretical chemistry

In order to evaluate the essence of the interactions of ginsenosides and proteins which are composed by α-amino acids, electrospray ionization mass spectrometry was employed to study the noncovalent interactions between ginsenosides (Rb₂, Rb₃, Re, Rg₁ and Rh₁) and 18 kinds of α-amino acids (Asp, Glu, Asn, Phe, Gln, Thr, Ser, Met, Trp, Val, Gly, Ile, Ala, Leu, Pro, His, Lys and Arg). The 1:1 and 2:1 noncovalent complexes of ginsenosides and amino acids were observed in the mass spectra. The dissociation constants for the noncovalent complexes were directly calculated based on peak intensities of ginsenosides and the noncovalent complexes in the mass spectra. Based on the dissociation constants, it can be concluded that the acidic and the basic amino acids, Asp, Glu, Lys and Arg, bound to ginsenosides more strongly than other amino acids. The experimental results were verified by theoretical calculations of parameters of noncovalent interaction between ginsenoside Re and Arg which served as a representative example. Two kinds of binding forms, “head–tail” (“H–T”) and “head–head” (“H–H”), were proposed to explain the interaction between ginsenosides and amino acids. And the interaction in “H–T” form was stronger than that in “H–H” form.     

Determining the Diastereoselectivity of the Formation of Dipeptidonucleotides by NMR Spectroscopy

Proteins are composed of l -amino acids, but nucleic acids and most oligosaccharides contain d -sugars as building blocks. It is interesting to ask whether this is a coincidence or a consequence of the functional interplay of these biomolecules. One reaction that provides an opportunity to study this interplay is the formation of phosphoramidate-linked peptido RNA from amino acids and ribonucleotides in aqueous condensation buffer. Here we report how the diastereoselectivity of the first peptide coupling of the peptido RNA pathway can be determined in situ by NMR spectroscopy. When a racemic mixture of an amino acid ester was allowed to react with an 5′-aminoacidyl nucleotide, diastereomeric ratios of up to 72 : 28 of the resulting dipeptido nucleotides were found by integration of ³¹P- or ¹H-NMR peaks. The highest diastereomeric excess was found for the homochiral coupling product d -Ser-d -Trp, phosphoramidate-linked to adenosine 5′-monophosphate with its d -ribose ring. When control reactions with an N-acetyl amino acid and valine methyl ester were run in organic solvent, the diastereoselectivity was found to be lower, with diastereomeric ratios≤62 : 38. The results from the exploratory study thus indicate that the ribonucleotide residue not only facilitates the coupling of lipophilic amino acids in aqueous medium but also the formation of a homochiral dipeptide. The methodology described here may be used to search for other stereoselective reactions that shed light on the origin of homochirality.     

Binary and ternary complexes of Cd(II) involving triethylenetetramine and selected amino acids and DNA units

The formation equilibria of the binary complex of cadmium(II) with triethylenetetramine (Trien) and of ternary complexes Cd(Trien)L, where L refers to amino acids, DNA constituents and related compounds have been investigated. Cd(II) was found to form a highly stable complex with Trien. The acid-base equilibria of Cd(Trien)²⁺ were characterized. Ternary complexes of amino acids and DNA constituents are formed through stepwise mechanism, whereby Trien binds to Cd(II), followed by interaction with ligand (L), whereas thiol-containing ligands form ternary complexes through a simultaneous mechanism. The formation constants of the complexes were determined at 25 °C and , = 0.1M NaNO₃. The participation of different ligand functional groups in the complex-formation was examined.