Protonation Constants Of Ligands Research Articles

AN ELECTROMETRIC METHOD FOR THE DETERMINATION OF IMPACT OF DMSO-WATER MIXTURES ON pKa VALUES OF SALICYLIC ACID DERIVATIVES

Objective: The main objective of this present study is to conduct an experiment to analyze the variation of protonation-deprotonation equilibria with regards to the dielectric constants of an organic medium, influence of errors on protonation constants and effect of pH on the percentage of species. Methods: The present investigation was carried out by using pH meter at a temperature of 303 K and ionic strength of 0.16 mol dm-3 in Dimethyl sulfoxide (DMSO)-water mixtures. The processing of data was done by using Gran plot titration. The advanced principles of mathematics and fuzzy logic have been employed to correlate chemical problems, known as chemometrics. To obtain best-fit chemical models, a modelling strategy such as SCPHD is used and a computer program MINIQUAD 75 is also employed for the refinement of results. Results: In the present study, we found the influence of dielectric constants of a medium Dimethyl sulfoxide (DMSO)-water on protonation constants of 5-Sulfosalicylic acid and 5-Hydroxysalicylic acid has been studied. The species distribution diagrams were presented and understood the effect of pH on the percentage of species. The obtained skewness values are ranging from 0.11-0.36 and–0.56-0.38, for 5-Sulfosalicylic acid (5-SSA) and 5-Hydroxysalicylic acid (5-HSA), respectively, which describes the distribution curves are right skewed and left skewed. The kurtosis values are ranging from 2.12-3.56, which indicates the peak of the distribution curve exhibits both platykurtic and leptokurtic pattern. The changes in the concentrations of some influential parameters such as log F, acid, alkali, volume of titrands, ligand causes variation of stability constants and the order of the effect of influential parameters on stability constants are as alkali>acid>ligand>volume of titrand>log F. Conclusion: It is observed that the significant influence of co-solvent Dimethyl sulfoxide (DMSO)-Water mixtures on the protonation constants of ligands also studied how some factors such as changes in concentrations of ligand, acid, base log F and volume of the solution have influence on the protonation constants.

Comparative paraCEST effect of amide and hydroxy groups in divalent cobalt and nickel complexes of tripyridine-based ligands.

Co(II) and Ni(II) complexes of two tri-pyridine-based ligands with two hydroxy and two amide exchangeable protons (TDTA) and with six amide exchangeable protons (TMTP) were investigated for application as paraCEST-based magnetic resonance imaging (MRI) contrast agents. The two hydroxy groups present in the TDTA ligand were found to be passive while the amide group was active towards the CEST process. In the case of the Co(II) and Ni(II) complexes of the TMTP ligand, all three coordinated amide groups participated in the exchange process, and excellent CEST signals were observed. The X-ray structure of the four complexes revealed the seven-coordinate geometry of Co(II) complexes and the six-coordinate geometry of Ni(II) complexes. The presence of amide protons and hydroxy protons in the complexes was detected by the NMR method. The stability of the complexes in solution at high temperatures, in different pH ranges and acidic conditions, in the presence of competing cations, and biologically relevant anions was investigated. Potentiometric titrations were carried out to determine the ligand's protonation constants and the complexes' thermodynamic stability constant at 25.0 °C and I = 0.15 mol L-1 NaClO4. ParaCEST studies of [Co(TMTP)]2+ and [Ni(TMTP)]2+ at variable pH and variable pulse power are highlighted.

Experimental and Molecular Modeling Studies on the Complexation of Chromium(III) with the Angiotensin-Converting Enzyme Inhibitor Captopril.

Captopril (CPT) is an inhibitor of angiotensin I converting enzyme, used as a medication for the treatment of people with high blood pressure, renal insufficiency, and cardiovascular diseases. It inhibits the angiogenesis process, vasoconstriction, and tumor metastasis. Some metal–captopril complexes exhibit antimicrobial activities. In the current work, the formation of the CrIII–CPT complex was studied spectrophotometrically and potentiometrically in aqueous solution. Kinetics of CrIII–CPT complex formation was spectrophotometrically studied over the pH range 3.20–4.20, at an ionic strength of 0.3 M at 30–50 °C. CrIII–CPT complex formation was potentiometrically studied at 25 °C, where ligand protonation constants and complexes’ overall stability constants were calculated. UV–vis absorption spectra were executed to confirm the complex formation. Density functional theory and molecular dynamics simulation were performed to search the geometries of the CrIII–CPT complex. Atoms in molecules and interaction region indicator calculations are used to investigate intermolecular interactions for the formation of CrIII–CPT complex. The antimicrobial activity of the CPT ligand and CrIII–CPT complex on the prevention and control of environmental pathogenic bacteria, as tested on both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli) via agar disc diffusion method, assess the ability to use as an antimicrobial agent. CPT had shown good antimicrobial activity against both types of bacteria, which had increased slightly the zone of inhibition in Cr-CPT that indicates the increased efficacy due to Cr(III) antimicrobial activity via its oxidative damage to the bacterial cell wall. No previous study tested the CPT antimicrobial activity against Gram-positive ones such as S. aureus

Speciation Study on O-Phosphorylethanolamine and O-Phosphorylcholine: Acid-Base Behavior and Mg2+ Interaction.

In the present study, the acid–base behavior of compounds constituting the headgroups of biomembranes, O-phosphorylethanolamine (PEA), and O-phosphorylcholine (PPC) was investigated by potentiometric titrations in NaCl aqueous solutions at different temperatures (15 ≤ t/°C ≤ 37) and ionic strength (0.15 ≤ I/mol L−1 ≤ 1) values. The complexation properties and the speciation of these ligands with Mg2+ were defined under different temperatures (15 ≤ t/°C ≤ 37) and I = 0.15 mol L−1. The results evidenced the formation of three species for PEA, namely, MLH2, MLH, and ML and two species for PPC, namely, MLH and ML. 1H-NMR titrations were performed on solutions containing ligand and metal–ligand solutions at t = 25°C and I = 0.15 mol L−1. The estimated values of ligand protonation and complex formation constants and the speciation model are in accordance with the potentiometric data. The enthalpy changes were also determined at t = 25°C and I = 0.15 mol L−1 by the dependence of formation constants on the temperature, confirming the electrostatic nature of the interactions. Matrix-assisted laser desorption mass spectrometry (MALDI-MS) was applied for the characterization of Mg2+-L systems (L = PEA or PCC). MS/MS spectra of free ligands and of Mg2+-L species were obtained. The observed fragmentation patterns of both Mg2+-L systems allowed elucidating the interaction mechanism that occurs via the phosphate group generating a four-membered cycle.

Complexes of cyclen side-bridged with a methylene-bis(phosphinate) group

A macrobicyclic cyclen-based ligand containing a geminal bis(phosphinate) N,N′-bridge was synthesized via a Mannich-type reaction. The other two macrocycle amine groups were modified with two acetate pendants, yielding ligand H4L. The cyclen-bis(phosphinate) intermediate, the ligand salt Na0.5(H5L)(H3.5L)Cl·20H2O and CuII complex Li2[Cu(L)]·4H2O were characterized by single-crystal X-ray diffraction. The ligand protonation constants and the stability constants of H4L complexes with Cu(II) and Zn(II) and lanthanide(III) ions were determined by potentiometry. The ligand protonation constants and the stability constants of H4L complexes with Cu(II) and Zn(II) ions are similar to those of H4dota. Conversely, the stabilities of its Ln(III) complexes are ~ 7–10 orders of magnitude lower than those of H4dota complexes due to steric restrictions of the methylene-bis(phosphinate) side bridge. Therefore, these findings indicate that the ligand H4L is suitable for the complexation of transition metal ions.

Neocuproine Copper(II) Complexes with Bioactive Ligands in Aqueous Solution

A potentiometric titration technique has been used to determine protonation constants of neocuproine {(neo): 2,9-dimethyl-1,10-phenanthroline} and bioactive ligands {(N,O-donor chelator, N,O): glycine (gly), leucine (leu), methionine (met), phenylalanine (phe), tyrosine (tyr), tryptophan (trp), asparagines (asn), glutamine (gln), aspartic acid (asp), glutamic acid (glu)} and their binary and ternary stability constants with copper(II) ion were determined at the constant ionic strength 0.1 M KCl and at 298.15 K. The protonation constants of neo and bioactive ligands and their stability constants of the binary and ternary copper(II) complexes were computed from the potentiometric titration data using BEST program. Furthermore, SPE program was used to determine the distribution of the species formed in solution medium. The stability of the ternary copper(II) complexes are compared with those of the corresponding the stability of the binary copper(II) complexes with regard to ΔlogK values.

Synthesis and Biological Evaluation of Novel Zn(II) and Cd(II) Schiff Base Complexes as Antimicrobial, Antifungal, and Antioxidant Agents

(E)-N,N-Dimethyl-2-((E-1-(2-(p-tolyl)hydrazono)propan-2-ylidene)hydrazine-1-carbothioamide (DMPTHP) and their Zn(II) and Cd(II) complexes have been synthesized and characterized. Different tools of analysis such as elemental analyses, IR, mass spectra, and 1H-NMR measurements were used to elucidate the structure of the synthesized compounds. According to these spectral results, the DMPTHP ligand behaved as a mononegatively charged tridentate anion. Modeling and docking studies were investigated and discussed. Novel Schiff base (DMPTHP) ligand protonation constants and their formation constants with Cd(II) and Zn(II) ions were measured in 50% DMSO solution at 15°C, 25°C, and 35°C at I = 0.1 mol·dm−3 NaNO3. The solution speciation of different species was measured in accordance with pH. Calculation and discussion of the thermodynamic parameters were achieved. Both log K1 and –ΔH1, for M(II)-thiosemicarbazone complexes were found to be somewhat larger than log K2 and –ΔH2, demonstrating a shift in the dentate character of DMPTHP from tridentate in 1 : 1 chelates to bidentate in 1 : 2; M : L chelates and steric hindrance were generated by addition of the 2nd molecule. The compounds prepared have significant activity as antioxidants, similar to ascorbic acid. It is hoped that the results will be beneficial to antimicrobial agent chemistry. The formed compounds acted as a potent antibacterial agent. Molecular docking studies were investigated and have proved that DMPTHP as antibacterial agents act on highly resistant strains of E. coli and also as an anticancer agent.

Structures, hydrolysis, stabilities of palladium(II) complexes containing biologically active ligands and species distribution in aqueous solution

[PdACl2](n-1)H2O complexes {A: 1,10-phenanthroline (phen), 4-methyl-phenanthroline (4-mphen), 5-methyl-1,10-phenanthroline (5-mphen), 4,7-dimethyl-1,10-phenanthroline (dmphen), 3,4,7,8-tetramethyl-1,10-phenanthroline (tmphen)} were synthesized and characterized by CHN elemental analysis, ATR-FT-MIR and ATR-FT-FIR, 1H NMR and 13C NMR spectral measurements. n is the number of crystal water molecules in the complexes. The n value for the complexes [Pd(phen)Cl2], [Pd(4-mphen)Cl2] and [Pd(5-mphen)Cl2] is 1; for the complex [Pd(tmphen)Cl2]H2O is 2; for the complex [Pd(dmphen)Cl2]2H2O is 3. [PdACl2](n-1)H2O complexes were converted into aqua complexes derived from 1,10-phenanthroline, [PdA(H2O)2]2+, and investigated [PdAB]+ mixed ligand complexes formed between [PdA(H2O)2]2+ complexes and amino acids {B: glycine (gly) and tyrosine (tyr)}. Protonation constants of the gly and tyr, the acid dissociation constants of the coordinated water molecules in [PdA(H2O)2]2+ complexes and the stepwise stability constant of the [PdAB]+ mixed ligand complexes were determined in aqueous 0.1 M KNO3 ionic media at 298.15 K by potentiometric methods. The protonation constants of ligands, the acid dissociation constants of aqua complexes and the stepwise stability constants of mixed ligand complexes were calculated from the potentiometric data using the “BEST” software package. The concentration distribution of the various species formed in aqueous solution was obtained using the “SPE” software package under the experimental conditions described. The order of stepwise stability of the mixed ligand complexes in terms of the gly and tyr was [Pd(tmphen)(gly/tyr)]+ > [Pd(dmphen)(gly/tyr)]+ > [Pd(4-mphen)(gly/tyr)]+ > [Pd(phen) (gly/tyr)]+ > [Pd(5-mphen)(gly/tyr)]+. This study could contribute to a better understanding of the behavior of the palladium(II) complexes in biological systems.

Complexation equilibria of ambroxol hydrochloride in solution by potentiometric and conductometric methods

The formation constants of Li(I), Mg(II), Sr(II), Ca(II), Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Ba(II), Pb(II), Al(III), Cr(III), Fe(III) and Th(IV) ions with ambroxol hydrochloride (AMB) were calculated using the half-n value. In presence of 0.1 M NaNO3, metal ions such as Zn(II), Cd(II), Ni(II), Cr(III), Li(I), Mg(II) and Al(III) forms three types of metal-ligand complexes (1:1, 1:2 and/or 1:3), while Sr(II) and Co(II) tend to form two types of metal complexes 1:1 and 1:2 (M:L). For ligand protonation constants, two logarithmic association constant values were calculated by the half-n method and are 10.7 and 7.6, respectively. The effect of ionic strength on stability constant of AMP, with different metal ions viz. Fe(III), Th(IV), Al(III), Cr(III) and Cu(II) was studied. Based on relationship between the ionic strength studied values and the 1st stability constants (Log K1H), we can conclude that the stability constants of the formed metal-ligand complex (1:1) were decreased as the ionic strength increased. The stoichiometry of the formed complexes in solution were determined by conductometric method and it is found to be of 1:1, 1:2 and/or 1:3 (M:L) complex species is formed in alkaline media. Also, study the species distribution diagrams of AMP for the calculated mole fraction αML and αML2 were discussed.

Levaquin drug complexing property towards platinum and palladium metal ions: Thermodynamic studies in aqueous solutions

The experimental protonation and complex formation equilibrium constants of levaquin (LFX) with platinum(II) and palladium(II) metal ions have been investigated at 310.15K in water solutions at ionic strength of I=0.16mol·dm−3 NaNO3 using pH-potentiometric and cyclic voltammetry techniques, and by means of Hyperquad 2008 estimation model program. Also, the dissociation constants of LFX and the equilibrium constants of its binary complexes with the studied platinum(II) and palladium(II) metal ions in I=0.16mol·dm−3 NaNO3 water solutions were observed at different temperatures such as 298.15, 310.15, 318.15 and 328.15K. The theoretical calculations of overall protonation and stability constants of the metal ion-LFX complex species in aqueous solutions were predicted as the free energy change associated with the LFX protonation, and metal ion – LFX complex formation equilibria using ab initio and density function theory calculations by applying Gaussian 09 software molecular modeling. The determination of equilibrium constants were confirmed by the spectrophotometric method with the refinement by using the HypSpec program. The usage of the experimental potentiometry/spectrophotometry techniques and theoretical predictions provides a complete picture of the microscopic equilibria of the studied systems (metal ions -LFX). Precisely, this theoretically predications could be useful to control the most real protonation constants of levaquin ligand in which the binding sites changes due to the ligand protonation/deprotonation equilibria. Also, the complexing capacities of different platinum(II) and palladium(II) metal ions towards LFX in solutions were evaluated and discussed. From the determined experimental stability constants of different metal complex species, the concentration distribution diagrams of the various metal ions - LFX complex species in solutions were estimated using HySS 2009 software.

Thermodynamic studies on metal ions – Ninhydrin – Glycine interactions in aqueous solutions

The experimental protonation and complex formation equilibrium constants of ligands (ninhydrin (NHN) and glycine (Gly)) with trivalent (iron(III), aluminium(III), and chromium (III)), divalent (copper(II), cobalt(II), nickel(II), strontium(II), manganese(II), and mercury(II)) and monovalent silver(I) metal ions have been investigated at 310.15 K in water solutions at ionic strength of 13.60 g·dm−3 NaNO3 using pH-potentiometric, UV–visible spectrophotometric, and cyclic voltammetry techniques, and by means of Hyperquad 2008 estimation model program. Also, the dissociation constants of NHN and the equilibrium constants of its binary complexes and ternary complexes with the studied metal ions in 13.60 g·dm−3 NaNO3 water solutions were observed at different temperatures such as (298.15, 310.15, 318.15 and 328.15) K. The theoretical calculations of overall protonation and stability constants of the metal ion-ninhydrin complex species in aqueous solutions were predicted as the free energy change associated with the ninhydrin protonation, and metal ion – ninhydrin – glycine complex formation equilibria using ab initio and density function theory calculations by applying Gaussian 09 software molecular modelling. The convention of the experimental Potentiometry/Spectrophotometry techniques and theoretical calculations provide a complete picture of the microscopic equilibria of the studied metal ions – ninhydrin – glycine systems. Precisely, this theoretical predication could be useful to control the most real protonation constants of ninhydrin and glycine ligands in which the binding sites change due to the ligand protonation/deprotonation equilibria. Also, the complexing capacities of different metal ions towards ninhydrin and glycine in solutions were evaluated and discussed. From the determined experimental stability constants of different metal complex species, the concentration distribution diagrams of the various metal ions – ninhydrin – glycine complex species in solutions were estimated using HySS 2009 software.

Nicotine – Metal ion interactions in solutions: Potentiometric, cyclic voltammetry investigations and quantum chemical calculations

The experimental protonation and complex formation equilibrium constants of nicotine (NIC) with trivalent (iron (III), and chromium (III)) and divalent (copper (II), and nickel (II)) metal ions have been investigated at 310.15 oK in water solutions at ionic strength of 13.60g·dm−3 NaNO3 using pH-potentiometric and cyclic voltammetry techniques, and by means of Hyperquad 2008 estimation model program. Also, the dissociation constants of NIC and the equilibrium constants of its binary complexes with the studied metal ions in 13.60g·dm−3 NaNO3 water solutions were observed at different temperatures such as (298.15, 310.15, 318.15 and 328.15) K. The theoretical calculations of overall protonation and stability constants of the metal ion-nicotine complex species in aqueous solutions were predicted as the Gibbs energy change associated with the nicotine protonation, and metal ion – nicotine complex formation equilibria using ab initio and density function theory calculations by applying Gaussian 09 software molecular modeling. The usage of the experimental potentiometry/spectrophotometry techniques and theoretical predictions provides a complete picture of the microscopic equilibria of the studied systems (metal ions -nicotinate). Precisely, this theoretically predications could be useful to control the most real protonation constants of nicotine ligand in which the binding sites changes due to the ligand protonation/deprotonation equilibria. Also, the complexing capacities of different metal ions towards nicotine in solutions were evaluated and discussed. From the determined experimental stability constants of different metal complex species, the concentration distribution diagrams of the various metal ions - nicotine complex species in solutions were estimated using HySS 2009 software.

Thermodynamic, Spectroscopic, and Computational Studies of f-Element Complexation by N-Hydroxyethyl-diethylenetriamine-N,N',N″,N″-tetraacetic Acid.

Potentiometric and spectroscopic techniques were combined with DFT calculations to probe the coordination environment and determine thermodynamic features of trivalent f-element complexation by N-hydroxyethyl-diethylenetriamine-N,N',N″,N″-tetraacetic acid, HEDTTA. Ligand protonation constants and lanthanide stability constants were determined using potentiometry. Five protonation constants were accessible in I = 2.0 M (H+/Na+)ClO4. UV-vis spectroscopy was used to determine stability constants for Nd3+ and Am3+ complexation with HEDTTA. Luminescence spectroscopy indicates two water molecules in the inner coordination sphere of the Eu/HEDTTA complex, suggesting HEDTTA is heptadentate. Luminescence data was supported by DFT calculations, which demonstrate that substitution of the acetate pendant arm by a N-hydroxyethyl group weakens the metal-nitrogen bond. This bond elongation is reflected in HEDTTA's ability to differentiate trivalent actinides from trivalent lanthanides. The trans-lanthanide Ln/HEDTTA complex stability trend is analogous to Ln/DTPA complexation; however, the loss of one chelate ring resulting from structural substitution weakens the complexation by ∼3 orders of magnitude. Successful separation of trivalent americium from trivalent lanthanides was demonstrated when HEDTTA was utilized as aqueous holdback complexant in a liquid-liquid system. Time-dependent extraction studies for HEDTTA were compared to diethylenetriamine-N,N,N',N″,N″-pentaacetic acid (DTPA) and N-hydroxyethyl-ethylenediamine-N,N',N'-triacetic acid (HEDTA). The results indicate substantially enhanced phase-transfer kinetic rates for mixtures containing HEDTTA.

Thermodynamic Studies of Trans-4-Hydroxy-L-Proline at Different Ionic Medium, Ionic Strength and Temperature

The aim of this work was to determine the solubility as well as the acidicconstants of trans-4-hydroxy-L-proline in 0.16 and 3.5 Mol.kg-1 NaClO4 and in 0.16 and 3.18 Mol.kg-1 NaCl at two different temperature, i.e. 298.15 and 310.15 K. trans-4-Hydroxy-L-proline, HL, is one of the most abundant amino acids present in collagen. As a major part of this protein, the measurement of hydroxyproline levels can be used as an indicator of collagen content. The protonation constants of ligand, K1 and K2, combined with the salting effects on the ligand in the ionic media were treated by the specific ion interaction theory, SIT, to give equilibrium constants at the infinite dilution reference state at 298.15 K and at 310.15 K, as well as specific interaction coefficients of the cation and anion of trans-4-hydroxy-L-proline with the media ions at the standard temperature, i.e. 298.15 K.

Complexation of Am(III) and Nd(III) by 1,10-Phenanthroline-2,9-Dicarboxylic Acid

The complexant 1,10-phenanthroline-2,9-dicarboxylic acid (PDA) is a planar tetradentate ligand that is more preorganized for metal complexation than its unconstrained analogue ethylendiiminodiacetic acid (EDDA). Furthermore, the backbone nitrogen atoms of PDA are aromatic, hence are softer than the aliphatic amines of EDDA. It has been hypothesized that PDA will selectively bond to trivalent actinides over lanthanides. In this report, the results of spectrophotometric studies of the complexation of Nd(III) and Am(III) by PDA are reported. Because the complexes are moderately stable, it was necessary to conduct these titrations using competitive equilibrium methods, competitive cation complexing between PDA and diethylenetriaminepentaacetic acid, and competition between ligand protonation and complex formation. Stability constants and ligand protonation constants were determined at 0.1 mol·L−1 ionic strength and at 0.5 mol·L−1 ionic strength nitrate media at 21 ± 1 °C. The stability constants are lower than those predicted from first principles and speciation calculations indicate that Am3+ selectivity over Nd3+ is less than that exhibited by 1,10-phenanthroline.

Synthesis, characterization, equilibrium study and biological activity of Cu(II), Ni(II) and Co(II) complexes of polydentate Schiff base ligand

Schiff base ligand, 1,4-bis[(2-hydroxybenzaldehyde)propyl]piperazine (BHPP), and its Cu(II), Ni(II) and Co(II) metal complexes were synthesized and characterized by elemental analysis, magnetic susceptibility, molar conductance and spectral (IR and UV–vis) studies. The ground state of BHPP ligand was investigated using the BUILDER module of MOE. Metal complexes are formed in the 1:1 (M:L) ratio as found from the elemental analysis and found to have the general formula [ML]·nH2O, where M=Co(II), Ni(II) and Cu(II), L=BHPP. In all the studied complexes, the (BHPP) ligand behaves as a hexadentate divalent anion with coordination involving the two azomethine nitrogen’s, the two nitrogen atoms of piperazine ring and the two deprotonated phenolic OH-groups. The magnetic and spectral data indicates octahedral geometry of metal(II) complexes. The ligand and their metal chelates have been screened for their antimicrobial activities using the disc diffusion method against the selected bacteria and fungi. They were found to be more active against Gram-positive than Gram-negative bacteria. Protonation constants of (BHPP) ligand and stability constants of its Cu2+, Co2+ and Ni2+ complexes were determined by potentiometric titration method in 50% DMSO–water solution at ionic strength of 0.1M sodium nitrate. It has been observed that the protonated Schiff base ligand (BHPP) have four protonation constants. The divalent metal ions Cu2+, Ni2+ and Co2+ form 1:1 complexes.

Complexation of Metal Ions with TRAP (1,4,7-Triazacyclononane Phosphinic Acid) Ligands and 1,4,7-Triazacyclononane-1,4,7-triacetic Acid: Phosphinate-Containing Ligands as Unique Chelators for Trivalent Gallium

Three phosphinic acid 1,4,7-triazacyclononane (TACN) derivatives bearing methylphosphinic (TRAP-H), methyl(phenyl)phosphinic (TRAP-Ph), or methyl(hydroxymethyl)phosphinic acid (TRAP-OH) pendant arms were investigated as members of a new family of efficient Ga(3+) chelators, TRAP ligands (triazacyclononane phosphinic acids). Stepwise protonation constants of ligands and stability constants of their complexes with Ga(3+), selected divalent metal, and Ln(3+) ions were determined by potentiometry. For comparison, equilibrium data for the metal ion-NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) systems were redetermined. These ligands exhibit high thermodynamic selectivity for Ga(3+) over the other metal ions (log K(GaL) - log K(ML) = 7-9) and a selective complexation of smaller Mg(2+) over Ca(2+). Stabilities of the Ga(3+) complexes are dependent on the basicity of the donor atoms: [Ga(NOTA)] (log K(GaL) = 29.6) > [Ga(TRAP-OH)] (log K(GaL) = 23.3) > [Ga(TRAP-H)] (log K(GaL) = 21.9). The [Ga(TRAP-OH)] complex exhibits unusual reversible rearrangement of the "in-cage" N(3)O(3) complex to the "out-of-cage" O(6) complex. The in-cage complex is present in acidic solutions, and at neutral pH, Ga(3+) ion binds hydroxide anion, induces deprotonation and coordination of the P-hydroxymethyl group(s), and moves out of the macrocyclic cavity; the hypothesis is supported by a combination of results from potentiometry, multinuclear nuclear magnetic resonance spectrometry, and density functional theory calculations. Isomerism of the phosphinate Ga(3+) complexes caused by a combination of the chelate ring conformation, the helicity of coordinated pendant arms, and the chirality of the coordinated phosphinate groups was observed. All Ga(3+) complexes are kinetically inert in both acidic and alkaline solutions. Complex formation studies in acidic solutions indicate that Ga(3+) complexes of the phosphinate ligands are formed quickly (minutes) and quantitatively even at pH <2. Compared to common Ga(3+) chelators (e.g., 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) derivatives), these novel ligands show fast complexation of Ga(3+) over a broad pH range. The discussed TRAP ligands are suitable alternatives for the development of (68)Ga radiopharmaceuticals.

Synthesis, spectroscopic characterization and thermal behavior of metal complexes formed with N′-(1-(4-hydroxyphenyl) ethylidene)-2-oxo-2-(phenylamino) acetohydrazide (H 3OPAH)

Complexes of Co(II), Ni(II), Cu(II), Mn(II), Cd(II), Zn(II), Hg(II) and U(IV)O 2 2+ with N′-(1-(4-hydroxyphenyl) ethylidene)-2-oxo-2-(phenylamino) acetohydrazide (H 3OPAH) are reported and have been characterized by various spectroscopic techniques like IR, UV–visible, 1H NMR and ESR as well as magnetic and thermal (TG and DTA) measurements. It is found that the ligand behaves as a neutral bidentate, monoanionic tridentate or tetradentate and dianionic tetradentate. An octahedral geometry for [Mn(H 3OPAH) 2Cl 2], [Co 2(H 2OPAH) 2Cl 2(H 2O) 4] and [(UO 2) 2(HOPAH)(OAc) 2(H 2O) 2] complexes, a square planar geometry for [Cu 2(H 2OPAH)Cl 3(H 2O)]H 2O complex, a tetrahedral structure for [Cd(H 3OPAH)Cl 2], [Zn(H 3OPAH)(OAc) 2] and [Hg(H 3OPAH)Cl 2]H 2O complexes. The binuclear [Ni 2(HOPAH)Cl 2(H 2O) 2]H 2O complex contains a mixed geometry of both tetrahedral and square planar structures. The protonation constants of ligand and stepwise stability constants of its complexes at 298, 308 and 318 K as well as the thermodynamic parameters are being calculated. The bond lengths, bond angles, HOMO, LUMO and dipole moments have been calculated to confirm the geometry of the ligand and the investigated complexes. Also, thermal properties and decomposition kinetics of all compounds are investigated. The interpretation, mathematical analysis and evaluation of kinetic parameters ( E a, A, Δ H, Δ S and Δ G) of all thermal decomposition stages have been evaluated using Coats–Redfern and Horowitz–Metzger methods.

Synthesis, spectral characterization, solution equilibria, in vitro antibacterial and cytotoxic activities of Cu(II), Ni(II), Mn(II), Co(II) and Zn(II) complexes with Schiff base derived from 5-bromosalicylaldehyde and 2-aminomethylthiophene

Schiff base namely 2-aminomethylthiophenyl-4-bromosalicylaldehyde (ATS)(4-bromo-2-(thiophen-2-yl-imino)methylphenol) and its metal complexes have been synthesized and characterized by elemental analyses, IR, 1H NMR, solid reflectance, magnetic moment, molar conductance, mass spectra, ESR and thermal analysis (TGA). The analytical data of the complexes show the formation of 1:2 [M:L] ratio of the formula [ML 2], where M represents Ni(II), Zn(II) and Cu(II) ions, while L represents the deprotonated Schiff base. IR spectra show that ATS is coordinated to the metal ions in a bidentate manner through azomethine-N and phenolic-oxygen groups. The ligand and their metal chelates have been screened for their antimicrobial activities using the disc diffusion method against the selected bacteria. A cytotoxicity of the compounds against colon (HCT116) and larynx (HEP2) cancer cells have been studied. Protonation constants of (ATS) ligand and stability constants of its Cu 2+, Co 2+, Mn 2+, Zn 2+ and Ni 2+ complexes were determined by potentiometric titration method in 50% (v/v) DMSO–water solution at ionic strength of 0.1 M NaNO 3.

Measurement of Magnesium Stability Constants of Biologically Relevant Ligands by Simultaneous Use of pH and Ion-Selective Electrodes

Simultaneous measurements with magnesium ion-selective and pH glass electrodes have been used for determination of the stability constants of magnesium ions with various biologically relevant ligands by alkalimetric titration under physiological conditions (37 ○C, I=0.15 mol⋅dm−3). New systems were investigated: magnesium with pyroglutamate, pyridoxine and HEPES, along with citrate, lactate, glycinate, aspartate and glutamate. For comparison, calcium stability constants with the same ligands were determined similarly, using calcium ion-selective and pH glass electrodes. Ligand protonation constants, necessary for the calculation of the metal complex formation constants, were also determined.