Thermodynamic studies of drug-alpha-cyclodextrin interactions in water at 298.15 K: promazine hydrochloride/chlorpromazine hydrochloride + alpha-cyclodextrin + H(2)O systems

Data on osmotic coefficients have been obtained for a binary aqueous solution of two drugs, namely, promazine hydrochloride (PZ) and chlorpromazine hydrochloride (CPZ) using a vapor pressure osmometer at 298.15 K. The observed critical micelle concentration (cmc) agrees excellently with the available literature data. The measurements are extended to aqueous ternary solutions containing fixed a concentration of alpha-cyclodextrin (alpha-CD) of 0.1 mol kg(-1) and varied concentrations (approximately 0.005-0.2 mol kg(-1)) of drugs at 298.15 K. It has been found that the cmc values increase by the addition of alpha-CD. The mean molal activity coefficients of the ions and the activity coefficient of alpha-CD in binary as well as ternary solutions were obtained, which have been further used to calculate the excess Gibbs free energies and transfer Gibbs free energies. The lowering of the activity coefficients of ions and of alpha-CD is attributed to the existence of host-guest (inclusion)-type complex equilibria. It is suggested that CPZ forms 2:1 and 1:1 complexed species with alpha-CD, while PZ forms only 1:1 complexed species. The salting constant (ks) values are determined at 298.15 K for promazine-alpha-CD and chlorpromazine-alpha-CD complexes, respectively, by following the method based on the application of the McMillan-Mayer theory of virial coefficients to transfer free energy data. It is noted that the presence of chlorine in the drug molecule imparts better complexing capacity, the effect of which gets attenuated as a result of hydrophobic interaction. The results are discussed from the point of view of associative equilibria before the cmc and complexed equilibria for binary and ternary solutions, respectively.     

Thermodynamic studies of molecular interactions in aqueous alpha-cyclodextrin solutions: application of McMillan-Mayer and Kirkwood-Buff theories

Osmotic vapor pressure and density measurements were made for aqueous alpha-cyclodextrin (alpha-CD) solutions in the temperature range between 293.15 and 313.15 K. The experimental osmotic coefficient data were used to determine the corresponding activity coefficients and the excess Gibbs free energy of solutions. Further, the activity data obtained at different temperatures along with the enthalpies of dissolution (reported in the literature) were processed to obtain the excess enthalpy and excess entropy values for the solution process. The partial molar entropies of water and of alpha-cyclodextrin were calculated at different temperatures and also at different concentrations of alpha-CD. Using the partial molar volume data at infinite dilution, the solute-solvent cluster integrals were evaluated which yielded information about solute-solvent interactions. The application of McMillan-Mayer theory of solutions was made to obtain osmotic second and third virial coefficients which were decomposed into attractive and repulsive contributions to solute-solute interactions. The second and third osmotic virial coefficients are positive and show minimum at 303.15 K. The Kirkwood-Buff (KB) integrals G(ij), defined by the equation G(ij) = f(infinity)0 (g(ij)- 1)4pir(2) dr, have been evaluated using the experimental osmotic coefficient (and hence activity coefficient) and partial molar volume data. The limiting values of KB integrals, G(ij)(0) are compared with molecular interaction parameters (solute-solute i.e., osmotic second virial coefficient) obtained using McMillan-Mayer theory of solutions. We found an excellent agreement between the two approaches.     

Volumetric Studies of 2,2,2-Cryptand in Aqueous and Aqueous KBr Solutions at 298.15 K: An Example Involving Solvent-Induced Hydrophilic and Hydrophobic Interactions

Density measurements of good precision are reported for aqueous and aqueous salt (KBr) solutions containing 2,2,2-cryptand (4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane) (~0.009 to ~0.24 mol·kg^?1) for the binary systems and for the ternary system with ~0.1 mol·kg^?1 2,2,2-cryptand and varying KBr concentrations (~0.06 to ~ 0.16 mol·kg^?1) at 298.15 K. The density data have been used to study the variation of apparent molar volume (\( \varphi_{V} \)) of 2,2,2-cryptand and of KBr as a function of concentration. 2,2,2-Cryptand is a diamine and hence it is hydrolyzed in aqueous solutions and needs an appropriate methodology to obtain meaningful thermodynamic properties. We have adopted a method of hydrolysis correction developed initially by Cabani et al. and later by Kaulgud et al. to analyze our volumetric data for the aqueous solutions. The method is described and we were successful in obtaining the limiting partial molar volume of the bare (free) cryptand in water at 298.15 K. Volumes of ionization as well as volumes of complexation (with KBr) are calculated. Estimations of the apparent molar volume of 2,2,2-cryptand in CCl₄ are also reported. There is a loss in volume for the cryptand on transferring it from CCl₄ to water. The volume changes due to ionization for the cryptand in water are calculated to be –20.5 and –0.6 cm³·mol^?1 for the mono- and di-protonation equilibria respectively, while the volume of complexation for K⁺ is +24.5 cm³·mol^?1. The results are discussed in terms of conformation, protonation equilibria and selective encapsulation of K⁺ ions in cryptand cavities. The solution volume properties seem to depend upon water–solute interaction as well on the solute–solute association because of hydrophobic interactions caused by lowering of the charge density on formation of cryptand-K⁺ species in solution.     

Synthesis,anti-leishmanial screening,molecular docking,and ADME study of 1-amidoalkyl 2-naphthol derivatives catalyzed by amino acid ionic liquid

Research on Chemical Intermediates - A series of amidoalkyl naphthol (AAN) derivatives have been synthesized by a one-pot multicomponent reaction of β naphthol, amide, and aromatic aldehydes...     

Thermodynamics of Aqueous Solutions of 18-Crown-6 at 298.15 K: Enthalpy and Entropy Effects

We reported previously activity and activity coefficient data for aqueous solutions of 18-crown-6 (18C6) in the concentration range of 0.1–2.0 mol-kg⁻¹ at 298.15 K. The results were interpreted in terms of the binding of four water molecules (two bridged and two singly H-bonded) inside the 18C6 cavity having a D_3d conformation. In this work, we report our thermodynamic analysis of the Gibbs energy and enthalpy data (obtained using enthalpy virial data from literature) in aqueous solutions of 18C6 at 298.15 K. The excess enthalpy and Gibbs energy parameters are computed and further used to obtain excess entropies of solutions as a function of 18C6 concentration. The same data are utilized to compute the partial molar entropies of solvent and solute at finite, as well as at infinite, dilution of 18C6 in water. It is observed that ΔG_mix, ΔH_mix and TΔS_mix values are all negative, whereas ΔG^E values show a slightly positive variation as a function of the 18C6 concentration. The partial molar excess entropy of water, ( , decreases (becomes negative) whereas that of 18C6, ( , increases with a increase in the 18C6 concentration. These results are explained in terms of various effects, which include water structure making, incorporation of water molecules in the crown cavities and crown–crown hydrophobic interactions, which persist even at the lowest concentration studied.     

Thermodynamic Equilibrium Constant Studies on Aqueous Electrolytic (Alkaline Earth Chlorides) Solutions Containing 18-Crown-6 at 298.15 K

Osmotic coefficient data have been obtained for the binary aqueous solutions of alkaline-earth chlorides (MgCl₂, CaCl₂ and BaCl₂) at 298.15 K using a vapor pressure osmometer. The measurements are extended to aqueous ternary solutions (containing a fixed concentration of 0.1 mol⋅kg⁻¹ 18-Crown-6 (18C6) having various electrolyte concentrations (0.01–0.2 mol⋅kg⁻¹). The mean activity coefficients of the ions and of 18C6 in binary and ternary solutions were obtained through calculations of activity and osmotic coefficient data. The lowering of activity coefficients of the ions and of 18C6 in ternary solutions is attributed to the presence of host-guest type equilibria due to complexation between them in the case of solutions containing Ca²⁺ and Ba²⁺ ions. The data are further subjected to scrutiny by applying the methodology developed by Patil and Dagade based on the McMillan-Mayer theory of solutions to obtain thermodynamic equilibrium constant values through transfer Gibbs energies. It is noted that the size of the crown cavity (diameter 0.266–0.32 nm), charge density of ions (i.e., coulombic interactions) as well as hydrophobic interaction play a major role in governing the occurrence and stability of the complexed species. The results are compared with those reported earlier for alkali-halides and 18C6 complexes and discussed further from the point of view of the importance of ion-pair formation equilibria in aqueous solutions.