Thermodynamics Of Complex Formation Research Articles

Thermodynamics of complex formation between aspartic acid and 2,3,4-pyridinecarboxylic acids in aqueous solutions

The present work reports on molecular interactions of dicarboxylic amino acid, L-aspartic acid (Asp), with nicotinic acid, isonicotinic acid and picolinic acid in aqueous solutions at 298.15 K. Thermodynamic parameters of complex formation between the reagents were estimated using solution calorimetry method. It was found that strengthening of the stability of the Asp complexes follows the order nicotinic acid < isonicotinic acid < picolinic acid. The process of complex formation between Asp and the pyridinecarboxylic acids in water is entropically favorable. For zwitterionic forms of reagents, DFT theoretical calculations at B3LYP/6-31++G(d,p) level of theory have been performed. Analysis of natural bond orbitals (NBO) has been carried out for the most stable conformers of complexes formed. According to the quantum chemical calculations and thermodynamic data, the complexes between Asp and pyridinecarboxylic acids with 1:2 stoichiometry is mainly formed due to the electrostatic interactions and hydrogen bonding.

Metal Chelation Therapy and Parkinson's Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs.

The present review reports a list of approximately 800 compounds which have been used, tested or proposed for Parkinson’s disease (PD) therapy in the year range 2014–2019 (April): name(s), chemical structure and references are given. Among these compounds, approximately 250 have possible or established metal-chelating properties towards Cu(II), Cu(I), Fe(III), Fe(II), Mn(II), and Zn(II), which are considered to be involved in metal dyshomeostasis during PD. Speciation information regarding the complexes formed by these ions and the 250 compounds has been collected or, if not experimentally available, has been estimated from similar molecules. Stoichiometries and stability constants of the complexes have been reported; values of the cologarithm of the concentration of free metal ion at equilibrium (pM), and of the dissociation constant Kd (both computed at pH = 7.4 and at total metal and ligand concentrations of 10−6 and 10−5 mol/L, respectively), charge and stoichiometry of the most abundant metal–ligand complexes existing at physiological conditions, have been obtained. A rigorous definition of the reported amounts is given, the possible usefulness of this data is described, and the need to characterize the metal–ligand speciation of PD drugs is underlined.

Thermodynamics of complex formation between hydroxypropyl-β-cyclodextrin and quercetin in water–ethanol solvents at T = 298.15 K

Quercetin (QCT) is a flavonoid possessing many activities, such as neuro-/cardioprotective, anti-inflammatory and anticancer, but its pharmacological application is severely curtailed by its low water solubility and in vivo bioavailability. The formation of a QCT–hydroxypropyl-β-cyclodextrin (HPβCD) host–guest complex is promising to improve QCT therapeutic potential. Therefore, here the heat effects of HPβCD solutions with QCT solutions in water–ethanol solvents at different concentrations were studied by calorimetric titration, and the stability of molecular complexes was assessed by UV–Vis spectrophotometry. Calorimetric titrations revealed the formation of a QCT/HPβCD host–guest complex with a stoichiometric ratio of 1:1 in X(EtOH) = 0.00, 0.05 and 0.10 molar fractions of solvents at pH = 7.0 and pH = 8.1. Thermodynamic parameters of the complex formation reaction (lgK; ΔrH; TΔrS) were obtained in these experimental conditions. Differently, no complex formation was noticed in water–ethanol mixed solvent when ethanol volume fraction exceeded 0.2 at neutral and alkaline pH, as well as a volume fraction higher than 0.1 at acidic pH. Furthermore, the results of differential scanning calorimetry tests run on dried HPβCD after dissolution in hydroalcoholic solutions indicated that ethanol and water compete for the complexation within the hydrophobic cavity of HPβCD. This explains the decreased QCT complexation efficacy in the presence of ethanol beyond 0.1 or 0.2 volume fraction.

Effect of the Solvent on the Coordination of Pyridine Derivatives with Zn Tetraphenylporphine

The coordination of zinc(II) tetraphenylporphine with pyridines was studied by electronic spectroscopy. Linear correlations were found between the thermodynamic and kinetic parameters of coordination in different solvents. The effect of the solvent on the stability constants of the complexes and the thermodynamics of complex formation are discussed.

X-ray crystallography, electrochemistry, spectral and thermal analysis of some tetradentate schiff base complexes and formation constant measurements

ABSTRACTA series of new transition metal Schiff base complexes was synthesized via the reaction of H2L (N,N′-bis(naphthylidene)-2-aminobenzylamine) with the transition metals (Cu2+, Co2+, Ni2+, Zn2+ and Mn2+) and characterized by elemental analysis, 1HNMR, FT-IR, UV-Vis spectroscopy, thermogravimetric analysis(TG) and in selected cases by X-ray crystallography. Thermodynamics of complex formation, electrochemistry of the metal Schiff base complexes and kinetic aspects of thermal decomposition of the complexes were also studied. The obtained formation constants change according to the following trend due to the electronegativity and Jahn-Teller effects of the central transition metals: Cu > Co > Ni > Zn >Mn. Cyclic voltammogram of the complexes in acetonitrile was done to evaluate the redox behavior of the complexes. Electrochemistry of these complexes showed a redox reaction without any successive reactions. Furthermore, kinetic parameters which calculated by Coats–Redfern equation revealed a first-order kinetics of thermal decomposition in all stages.

Thermodynamics of complex formation between Cu(II) and glycyl–glycyl–glycine in water–ethanol and water–dimethylsulfoxide solvents

The paper provides an overview of own data on complex formation between Cu(II) and glycyl–glycyl–glycine in water and water–organic mixed solvents. Calorimetric and potentiometric methods were employed for the study of complex formation between Cu(II) with zwitterion of glycyl–glycyl–glycine and anion of glycyl–glycyl–glycine in water–ethanol and water–dimethylsulfoxide solvents. Stability of [CuHL]2+ and [CuL]+ grows with increase in concentration of both non-aqueous components in solvents. A monotonic increase in the exothermicity of [CuHL]2+ complexation with the addition of ethanol to water was observed. The enthalpy of [CuL]+ complex formation has changed with an exothermic peak at 0.1 ÷ 0.3 mol fractions of ethanol. The main solvation contributions which control the exothermicity increasing of [CuL]+ complex formation reaction and the stability of [CuHL]2+ in H2O–EtOH solvent were not established. However, the resolvation of ligands is the key factor for growth of the stability of both [CuHL]2+ and [CuL]+ complexes in H2O–DMSO solvent as well as the stability of [CuL]+ and the exothermicity of [CuHL]2+ complex formation in H2O–EtOH mixtures. Proper data are compared with data reported in the literature.

MOLECULAR COMPLEXES OF SULPHUR DIOXIDE WITH N,O-CONTAINING ORGANIC BASES (REVIEW)

The literature data on the synthesis, stoichiometry, structure and relative stability of molecular complexes of sulphur dioxide with N,O-containing organic bases have been systematized and generalized. It was shown that the yield of the reaction product of sulfur dioxide with organic bases (such as amines) are strongly influenced by the conditions of synthesis: the nature of the solvent (basicity, polarity), the temperature and SO2:L ratio in the reaction medium. The stoichiometry of SO2*nL molecular complexes depends on ligand denticity, as well as its ability to H-bonding. The reaction of the sulfur oxide (IV) with organic bases can give S←N and S←O complexes. With the increase of the value of base proton affinity the decrease ΔrSN values has been marked. Characteristic parameter Δr SN = r SN – a1(rS+ rN) (where rSNis the S←N donor-acceptor bond length) has been determined by microwave spectroscopy and X-ray analysis, rSand rNwere the tabulated values of the homopolar covalent radii of sulphur and nitrogen heteroatoms. The dependence of formation enthalpy of molecular complexes of basic amines and spectral characteristics has been noted; enthalpy-entropy compensation for S←N and S←O complex-es has been stated. Despite the limited experimental data on the thermodynamics of complex formation and the lengths of donor-acceptor bonds for the same compounds it has been found bond S←N strength in SO2 molecular complexes to depend on the intrinsic value of ΔrSN. The contribution of van der Waals forces and charge transfer forces to the formation of molecular complexes of sulphur dioxide has been stated.

Alumazene adducts with acetonitrile: Structure and thermal stability

Lewis acid-base adducts of the “inorganic analog of benzene” alumazene [{2,6-(i-Pr)2C6H3NAlMe}3] (1) with acetonitrile (CH3CN, acn) and deuteroacetonitrile (CD3CN, d3-acn) were synthesized, spectroscopically characterized, and their molecular structures were elucidated by the X-ray diffraction analysis as a bis-adduct 1(acn)2 and a tris-adduct 1(d3-acn)3. The thermodynamics of complex formation was investigated experimentally and theoretically. Thermodynamic characteristics of process 1(acn)3·acn (s) = 1(acn)2 (s) + 2 acn (g) in the temperature range 294–370 K have been derived from the vapor pressure–temperature dependence measurements by the static tensimetric method. It is shown that above 435 K in the presence of 1 gaseous acn undergoes irreversible polymerization reaction. Quantum chemical computations at B3LYP/6-311G(d,p) level of theory have been performed for the 1(acn)n and model complexes of [(HAlNH)3] (1m), 1m(acn)n (n = 1–3). Obtained results indicate that for the gas phase adducts upon increasing the number of acn ligands the donor-acceptor Al–N(acn) distances increase in accord with decrease of the donor-acceptor bond dissociation energies.

Hydration Differences Explain the Large Variations in the Complexation Thermodynamics of Modified γ-Cyclodextrins with Bile Salts.

The structure and thermodynamics of inclusion complexes of seven different γ-cyclodextrins (γCDs) and three biologically relevant bile salts (BS) were investigated in the present study. Natural γCD and six modified γCDs [two methyl-γCDs, one sulfobutyl ether-γCD (SBEγCD), and three 2-hydroxypropyl-γCDs (HPγCD)] and their complexes with BS were investigated by isothermal titration calorimetry, NMR, and molecular dynamics simulations. With the exception of the fully methylated γCD, which did not bind the BSs investigated, all of the γCDs formed 1:1 complexes with the BS, and the structures were similar to those with natural γCD; i.e., the modifications of the γCD had limited structural impact on the formation of complexes. Isothermal titration calorimetry was carried out over in the temperature interval 5-55 °C to enable the calculation of the stability constant (K) and the thermodynamic parameters enthalpy (ΔH°), entropy (ΔS°), and heat capacity (ΔCp°). The stability constants decreased with an increased degree of substitution (DS), with methyl substituents having a lower effect on the stability constant than the sulfobutyl ether and hydroxypropyl substituents on the stability constants. Enthalpy-entropy compensation was observed, since both enthalpy and entropy increased with the degree of substitution, which may reflect dehydration of the hydrophobic surface on both CD and BS. Calculations based on ΔCp° data suggested that each of the substituents dehydrated 10-20 (hydroxypropyl), 22-33 (sulfobutyl ether), and 10-15 Å(2) (methyl) of the BS surface area, in reasonable agreement with estimates from the molecular dynamics simulations. Combined with earlier investigations on modified βCDs, these results indicate general trends of the substituents on the thermodynamics of complex formation.

Study of thermodynamics of complex formation of flavonoids of steviа (Stevіa rebaudіana Bertonі) leaves

Scientists have studied the mechanisms of forming complexes between flavonoids of different plants and ions of iron and copper. Stevia is one of many plants, rich in biologically active substances and which is practically uninvestigated. In particular, the antioxidant effect of flavonoids of stevia leaves is not studied and there are no data on its thermodynamic properties, namely the possibility of natural flow of the complex formation process. There are no data on the possibility of forming the complex of flavonoids with aluminum ions. Taking into account that the dried leaves of stevia (Stevia rebaudiana Berton) is a rich source of flavonoids, their antioxidant action was studied based on thermodynamic researches. It is determined that 65% of flavonoids of stevia leaves are involved in forming the complex with aluminum ions. The degree of complex formation of the flavonoids of the leaves of stevia, grown in different agro-climatic zones of Ukraine was calculated. The Gibbs energy of stevia flavonoids is 12,8-13,8 that indicates the natural flow of the complex formation process. Stability constant of the formed complex is 250.6 l/mol. It was determined that the stevia leaves are a rich source of flavonoids, which take active part in the complex formation and show antioxidant effect. The obtained research results have become the basis for the developed nomogram, which allows to speed up defining the complex formation degree depending on the content of flavonoids in stevia leaves.

Thermodynamics of complexes formation by ITC in methanol/water=9/1 (v/v) solution: A case study

Abstract Most enzymes that participate in the biochemistry of nucleic acids require divalent metal ion cofactors to promote activity. Development of potent inhibitors, acting against those viral enzymes operating via a cooperative two-metal ion mechanism, such as HIV integrase (IN) and RNase H, hepatitis C virus polymerase and influenza endonuclease, requires optimizing the binding affinity to the target, which is dictated by the binding free energy composed of both enthalpic and entropic contributions. They can be obtained by using isothermal titration microcalorimetry. We have defined an experimental procedure for obtaining reliable thermodynamic data in methanol/water = 9/1 0.1 M KCl as solvent, used to overcome solubility problems. In this way we have measured the heats of formation of the complexes formed by N-(4-fluorobenzyl)-5-hydroxy-2-isopropyl-1-methyl-6-oxo-1,6-dihydroxypyrimidine-4-carboxylate (HL, a model of Raltegravir, the antiretroviral drug produced by Merck & Co.), and a series of divalent metal ions of biological interest (Mg(II), Mn(II), Co(II) and Zn(II)), whose speciation was previously determined by potentiometry.

Complexation of cyclodextrins with flavines in aqueous solutions

Data on the binding mode and thermodynamics of complex formation for various cyclodextrins (CDs) with flavines are summarized. It is shown that the governing factors of complexation are the size, degree of hydration, and hydrophobicity of the guest molecule. It is found that the presence of small hydrophobic substituents in a flavine’s structure increases their affinity toward cyclodextrin cavities, raising the stability of a complex. In contrast, the presence of bulky and polar side groups in a flavine’s structure prevents its inclusion in a macrocyclic cavity and weakens complexation. The size of a CD cavity plays a minor role in the interaction between CDs and flavines, since the inclusion of a guest molecule is only partial.

A DFT analysis of the effect of chelate ring size on metal ion selectivity in complexes of polyamine ligands

DFT calculations were carried out using the dmol3 program to investigate the thermodynamics of complex formation of polyamine complexes of M(II) ions (M=metal) in the gas-phase, and in aqueous solution, where the cosmo module of dmol3 models aqueous solution as a structureless dielectric medium with a dielectric constant appropriate for water. The calculations that included relativistic effects employed the all electron scalar relativity option available in dmol3. The values of ΔH(aq)(DFT) and ΔG(aq)(DFT) for reactions such as [M(H2O)6]2++en=[M(H2O)4en]2++2H2O (en=ethylenediamine) in aqueous solution for M=Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, and Cd were found to correlate well with the corresponding values in aqueous solution. Values of ΔH(g)(DFT) for reactions such as [M(H2O)4en]2++tn=[M(H2O)4tn]2++en (tn=1,3-diaminopropane) calculated in the gas-phase for M=Ca, Cr,…Cu showed the effect of changing chelate ring size from 5-membered for en to 6-membered for tn in that complexes of smaller metal ions such as Cu(II) were less destabilized by the increase in chelate ring size than larger metal ions such as Ca(II). This supports the chelate ring-size rule (R.D. Hancock, A.E. Martell, Chem. Rev. 89 (1989) 1875) that states that increase of chelate ring size stabilizes the complexes of smaller metal ions relative to those of larger metal ions. Use of cosmo to simulate the change from the en to the tn complexes in aqueous solution showed only a small response to change in metal ion size, as is found to be the case experimentally. An important aspect here is that the change in logK1 on changing chelate ring size in passing en to tn complexes is of the same order of magnitude as the probable uncertainty in the energies obtained from the DFT calculations. The DFT calculations show how aqueous solution dampens out chelate effects for small ligands such as en and tn, and also removes the effects of polarizability seen in the gas-phase. The chelate ring size rule is supported by calculations on Ni(II) complexes of pairs of polyamine ligands such as dien (diethylenetriamine) and dptn (1,5,9-triazanonane), or trien (triethylenetetramine) and 2,3,2-tet (1,4,8,11-tetraazaundecane), where the first member of the pair of ligands forms only 5-membered chelate rings, while the second member forms at least one 6-membered chelate ring in place of a 5-membered chelate ring formed by the first member. The DFT calculations show that increase of chelate ring size usually leads to a decrease in stability of the Ni(II) complex, but correctly predict that the 2,3,2-tet complex will be more stable than the trien complex, which is an unusual example where replacing a 5-membered chelate ring with a 6-membered chelate ring leads to higher complex stability. The role of polarizability effects in the thermodynamics of complex-formation is discussed. Polarizability effects stabilize complexes of larger ligands such as dptn relative to those of smaller analogs such as dien in the gas-phase by more effectively dispersing the cationic charge over the complex. Also discussed is the possible role of specific solvation by water molecules in the thermodynamics of complex-formation in aqueous solution, which effect is not taken into account by the cosmo module used in this paper.

The influence of water–ethanol mixture on the thermodynamics of complex formation between 18-crown-6 ether and l-phenylalanine

The influence of water–ethanol mixture composition on the complex formation between 18-crown-6 ether and l-phenylalanine was studied by titration calorimetry at Т=298.15K. The standard thermodynamic parameters (ΔrGо, ΔrHо, ТΔrSо) of formation of [Phe18C6] molecular complex were calculated from data obtained by means of the microcalorimetric system TAM III (TA Instruments, USA) at X(EtOH)=0.0/0.6mol fraction. The stability of [Phe18C6] and the mechanism of complexation in water were investigated using the 1Н and 13С NMR spectroscopy. The increase of EtOH concentration results in an increase of the complex stability and of the exothermicity of complexation.

Tetradentate schiff base ligands of 3,4- diaminobenzophenone: Synthesis, characterization and thermodynamics of complex formation with Ni(II), Cu(II) and Zn(II) metal ions

Some new symmetrical diimino tetradentate Schiff base ligands were synthesized by the reaction of 3,4-diaminobenzophenone with salicylaldehyde derivatives, such as [N,N?-bis(4-methoxysalicylaldehyde)- 3,4-diaminobenzophenone] (L1), [N,N?-bis(5-methoxysalicylaldehyde)- 3,4-diaminobenzophenone] (L2), [N,N?-bis(5-bromosalicylaldehyde)-3,4- diaminobenzophenone] (L3), [N,N?-bis(5-nitrosalicylaldehyde)-3,4- diaminobenzophenone] (L4). Additionally, a tetradentate Schiff base ligand [N,N?-bis(3-methoxysalicylaldehyde)-3,4-diaminobenzophenone] (L5), was synthesized. All the Schiff bases and their Ni(II), Cu(II) and Zn(II) complexes were characterized using elemental analysis and infrared, electronic, mass and 1H-NMR spectroscopy. The formation constants of the complexes were measured using UV-Vis spectroscopic titration at constant ionic strength 0.1 M (NaClO4), at 25?C in dimethylformamide (DMF) as solvent.

Thermodynamics of complex formation in mixed solvents K and ΔH for the formation reaction of [Gly18C6] at 298.15 K

The influence of H2O–EtOH and H2O–Acetone mixed solvents at various compositions on the thermodynamics of complex formation reaction between crown ether 18-crown-6 (18C6) and glycine (Gly) was studied. The standard thermodynamic parameters of the complex [Gly18C6] (log K°, ΔrH°, ΔrS°) were calculated from thermochemical data at 298.15 K obtained by titration calorimetry. The complex stability and its formation enthalpy increase with increasing the non aqueous component concentration in both mixed solvents. The thermodynamic data were discussed on the basis of the solvation thermodynamic approach and the solvation contributions of the reagents and of the complex to the complex stability were analyzed.

31P NMR study of the stoichiometry, stability and thermodynamics of complex formation between palladium(II) acetate and bis(diphenylphosphino)ferrocene

The complexation reaction between palladium (II) acetate, and 1,1′-bis(diphenylphosphino)ferrocene, DPPF, was investigated in two different deuterated solvents CDCl 3 and DMSO at various temperatures using 31P NMR spectroscopy. The exchange between free and complexed DPPF is slow on the NMR time scale and consequently, two 31P NMR signals were observed. At metal ion-to-ligand mole ratio larger than 1, only one 31P NMR signal was observed, indicating the formation of a 1:1 Pd 2+–DPPF complex in solution. The formation constant of the resulting 1:1 complexes was determined from the integration of two 31P signals. The values of the thermodynamic parameters (Δ H, Δ S and Δ G 298) for complexation were determined from the temperature dependence of stability constants. It was found that, in both solvents, the resulting complex is mainly entirely enthalpy stabilized and the Δ H compensates the TΔ S contribution.

Solvent effect on the thermodynamics of Ag(I) coordination to tripodal polypyridine ligands

An investigation on the thermodynamics of complex formation between Ag(I) ion and two tripodal ligands tris[(2-pyridyl)methyl]amine (TPA) and 6,6′-bis-[bis-(2-pyridylmethyl)aminomethyl]-2,2′-bipyridine (BTPA) has been carried out in the aprotic solvents dimethylsulfoxide (DMSO) and dimethylformamide (DMF) by means of potentiometry and titration calorimetry. The results for TPA are compared with those already obtained for other aliphatic tripodal polyamines. In general, the TPA ligand forms complexes less stable than 2,2′,2″-triaminotriethylamine (TREN) and tris(2-(methylamino)ethyl)amine (Me3TREN) as a result of the combination of higher structural rigidity of TPA and lower σ-donor ability of pyridinic moieties with respect to primary and secondary amines. The same trend is found if the stability of Ag(I) complex with TPA is compared with that of tris(2-(dimethylamino)ethyl)amine (ME6TREN), despite the pyridinic nitrogen is formally a tertiary one. Theoretical calculations run to explain the reasons of this weaker interaction indicate that this difference is due to solvation, rather than to steric or σ-donor effects. The ligand BTPA is able to form bimetallic species whose relative stability is largely influenced by the different solvation of Ag(I) ion in DMSO and DMF rather than by the difference in the dielectric constants of these two media.

Thermodynamics of complex formation in ionic liquids: cesium complexes with 18-crown-6

Thermodynamic data for the formation of cesium complexes with 18-crown-6 (18C6, L) [Cs(18C6)] + in N -butyl-4-methyl- pyridinium tetrafluoroborate, 1-butyl-3-methylimidazolium tetrafluoroborate and 1-butyl-3-methylimidazolium dicyanamide, measured using 133 Cs NMR spectroscopy at 23–50 C, revealed that the stability of cesium complex in ionic liquids is affected by the nature of both cation and anion of room temperature ionic liquid and is in the range between the values found for water and DMF.

Kinetics and thermodynamics of complex formation with iron of a new series of dicatecholspermidine siderophore-like ligands

This article deals with the kinetics and thermodynamics of complex formation between Fe3+ and a series of four synthetic chelators of the 1,2-dicatecholspermidine family (LA5, LA3, LE5 and LE3). LA5 and LA3 bear a carboxylic moiety linked to the central nitrogen by either a C5 or a C3 chain, whereas LE5 and LE3 bear an ethyl ester moiety. The following data concern LE5, LE3, LA5 and LA3, respectively. Each species undergoes four acid-base dissociations of the hydroxyls of the catechols with, for the two hydroxyls in position 1; average pK2a=7.30, 7.25, 7.45, 7.34 and, for the two hydroxyl in position 2; average pK3a=12.35, 12.65, 12.10, 12.60. The LA5 and LA3 species also undergo proton-dissociations of their carboxylic moieties; pK1a=5.20 and 5.10. The four species form one-to-one iron complexes with, for the 1-hydroxyl; an average pK22a=2.65, 2.25, 2.95, 2.80, for the 2-hydroxyl; pK33a=5.20, 5.40, 6.10, 5.40 and, for the carboxylic moieties; pK11a=3.90 and 4.45. In the vicinity of pH 5, Fe3+ is rapidly exchanged between FeNta and the four ligands. This occurs with direct rate constants: k1=(1.3±0.1)×104, (1.4±0.2)×104, (3.3±0.2)×104, (1.4±0.1)×104M−1s−1, and reverse rate constants: k−1=(7±0.5)×104, (9±1)×104, (1.15±0.15)×105, (7±0.5)×104M−1s−1. The kinetic data, the pKa values of the free ligands, those of the iron complexes and the β value of FeNta allow us to determine the affinity constants of the four ligands for iron: logβ1=33, 34, 33, 34, and pFe=23.3, 24.6, 22.2, 24.3. This implies that these ligands of the dicatecholspermidine family may act as siderophores. They may also be used as drug carriers which can utilize the bacterial iron-acquisition paths.