Enthalpy-entropy Compensation Plots Research Articles

Aggregation behavior and thermodynamic parameters of biosurfactants (NaC/NaDC) in aqueous medium of Emtricitabine and Lamivudine (anti-HIV drugs)

Abstract This paper investigates the interactions and aggregation behavior of biosurfactants, sodium cholate (NaC) and sodium deoxycholate (NaDC) in aqueous solutions of Emtricitabine and Lamivudine (anti-HIV drugs). The study uses conductometry and UV–visible spectroscopy techniques to evaluate the critical micelle concentration (CMC) at different temperatures ranging from 298.15 K to 313.15 K with a variation of 5 K. The temperature dependence of the CMC was examined, and the stability of micelles was analyzed in light of the hydrophobic-hydrophilic interactions involved in this system. The CMC obtained from both the methods are in agreement. Various thermodynamic parameters, such as ∆ H m 0 ${\increment}{H}_{m}^{0}$ , ∆ S m 0 ${\increment}{S}_{m}^{0\hspace{0.17em}}$ and ∆ G m 0 ${\increment}{G}_{m}^{0}$ have been estimated using a “pseudo-phase separation model” to understand the contribution of the chemical and de-solvation part in the micellization process. Furthermore, the enthalpy-entropy compensation plots validate the micellar stability of the studied systems.

Comparative Effect of Physiological Salts upon Micellization of T1304 and T1307.

We present a comprehensive investigation on the interaction of tetronics (T1304 and T1307) with some important physiological salts (NaH2PO4, KH2PO4, Na2CO3, NaCl, and KI). Thermodynamic and microstructural aspects of these interactions were studied as a function of the solution temperature, pH and salt concentration. Characterizations were performed using turbidimetric, calorimetric, and scattering techniques. We show that, at ambient temperature, T1304 molecules aggregated to form spherical core-shell aggregates displaying a unimodal distribution pattern. On the other hand, unimers and large clusters dominated in the case of highly hydrophilic T1307. Its micellization was promoted in the presence of salts as per the following trend: NaCl < KH2PO4 < NaH2PO4 ≪ Na2CO3. Aggregation was found to be endothermic, and hydrophobic interactions (TΔSmic > ΔHmic) prevailed. The enthalpy-entropy compensation plot was found to be linear for both copolymers. Demicellization occurred in the presence of KI as it facilitated the buildup of water structures around the copolymer chains. This could be verified from the increase in the cloud point, critical micelle concentration, and free energy. Overall, the temperature and salts inflicted a stronger hydrophobic effect upon T1304 in comparison to T1307.

Current Status of Enthalpy–Entropy Compensation Phenomenon

For similar physical–chemical processes in chemistry and biology, the phenomenon of linear enthalpy– entropy compensation (EEC) is a thermodynamic puzzle remaining unexplained for a long time. The basic thermodynamic rules do not rigorously support the EEC phenomenon. In some restricted conditions EEC may appear linear with nonrealistic (i.e. hypothetical) values of the slope (the compensation temperature), and the intercept (the compensation free energy). The compensation temperature (Tcomp) is normally higher than the experimental temperature. Compensation temperature may even become negative, and the related phenomenon is called anti-enthalpy–entropy compensation (AEEC). Negative Tcomp is unrealistic. Both EEC and AEEC are not explainable; the derived Tcomp and ΔGcomp (free energy of compensation) of the EEC plot are impractical. The neglect of the Gibbs free energy changes (of similar processes in the EEC plot) makes the phenomenon arbitrary. In a restricted condition (i.e. narrow free energy window range) linear compensation is an assumed solution. In overall consideration, the reported correlations are physicochemically uncertain. The said compensation may arise for both kinetic and equilibrium processes. The manifestations are nearly same. Our demonstration and discussion in this paper pertain to equilibrium processes.

Induced-Dipole-Directed, Cooperative Self-Assembly of a Benzotrithiophene.

A benzotrithiophene derivative possessing phenylisoxazoles self-assembled to form stacks. The molecule isodesmically self-assembled in chloroform, whereas it self-assembled in a cooperative fashion in decalin and in methylcyclohexane. Thermodynamic studies based on isodesmic, van der Schoot, and Goldstein-Stryer mathematical models revealed that the self-assembly processes are enthalpically driven and entropically opposed. An enthalpy-entropy compensation plot indicates that the assembly processes in chloroform, decalin, and methylcyclohexane are closely related. The enthalpic gains in less-polar solvents are greater than those in more-polar solvents, resulting in the formation of large assemblies in decalin and in methylcyclohexane. The formation of large assemblies leads to cooperative assemblies. The elongation process is enthalpically more favored than the nucleation process, which drives the cooperativity of the self-assembly. DFT calculations suggested that a hexameric assembly is more stable than tetrameric or dimeric assemblies. Cooperative self-assemblies based on intermolecular interactions other than hydrogen bonding have rarely been reported. It is demonstrated herein that van der Waals interactions, including induced dipole-dipole interactions, can drive the cooperative assembly of planar π-conjugated molecules.

Solubility of α-glycine in water with additives at a temperature range of (293.15–343.15) K: Experimental data and results of thermodynamic modeling

The solubility of α-glycine in water with different additives (sodium nitrate, ammonium nitrate, ammonium sulfate, and ammonium chloride) was measured under atmospheric pressure across the temperature range of (293.15–343.15) K at intervals of 10.00 K using a dynamic laser method. Solubility was found to increase with increasing temperature and additive level. The experimental data were correlated with the modified Apelblat model, nonrandom two-liquid model (NRTL), and λh model. The R2 of the fitting regression indicated good applicability of these models to the glycine solubility data in the studied systems (R2 > 0.99). Apparent standard enthalpy, entropy, and Gibbs free energy changes of the solution were calculated based on the van't Hoff equation to elucidate the dissolution mechanism. The results showed that the dissolving process of glycine was endothermic, and the main dissolution driving force contributor was enthalpy in all the additive + water systems studied. By means of enthalpy-entropy compensation analysis, a non linear ΔHsolΘ versus ΔGsolΘ enthalpy-entropy compensation plot with positive and negative slopes was obtained for the systems studied. The evaluated values of HE showed that the mixing process of α-glycine in all the systems studied was exothermic.

Enthalpy-Entropy Compensation (EEC) Effect: Decisive Role of Free Energy.

The "enthalpy-entropy compensation" (EEC) effect has been a long-standing fascinating yet unresolved phenomenon in chemical thermodynamics. The reasons for the observation of EEC are not clear. Various views such as empirical, extrathermodynamic, error-related, solvation, and so forth as reasons for the H/S linear correlation are floating. Statistical reasons and a hidden Carnot's cycle (involving microscopic "heating and cooling" machines) have also been proposed recently for the observation of EEC. In this work, we have attempted a different line of approach to understand and explain the phenomenon. In the EEC treatment, the enthalpy (ΔH) and entropy (ΔS) values of "similar processes" are considered keeping aside the role of the other important thermodynamic parameter, that is, the free energy (ΔG). Considering ΔG along with ΔH and ΔS, it is established that the conventional EEC plot is not appropriate and mathematically sound. Consideration of ΔG may account for correlations of different kinds, linear, nonlinear, and so forth. Reports of non- or anticompensation phenomenon also prevail in the literature. A realistic account of the role of ΔG along with ΔH and ΔS in the understanding of such EEC correlations using authentic literature data is presented and discussed herein. EEC has several facets. Planned studies on similar systems with a wide range of ΔG values are required for realistic evaluation of the EEC and antienthalpy entropy compensation manifestations.

Unravelling the binding energetics of a synthetic polymeric heparin antidote with heparin using isothermal titration calorimetry

Unravelling the binding energetics of a synthetic polymeric heparin antidote with heparin using isothermal titration calorimetry

Micellisation and thermodynamic properties of sodium dodecyl sulphate in water-1,2-alkanediol co-solvents: chain length effect

Effects of varying concentrations of 1,2-ethanediol, 1,2-butanediol and 1,2-hexanediol (glycols) on the micellisation and thermodynamic properties of sodium dodecyl sulphate (SDS) were studied at temperature range 288–313 K by conductometry method. Critical micelle concentration (CMC) of SDS increased in 1,2-ethanediol but decreased in the longer carbon chain glycols in the order: 1,2-hexanediol < 1,2-butanediol < pure water < 1,2-ethanediol. As temperature increased, CMC of SDS increased linearly in 1,2-ethanediol. Conversely, minimum CMC values were observed in 1,2-butanediol and 1,2- hexanediol between 293 K and 303 K at the temperature range studied, indicating more ordered water structure is favoured by the longer hydrocarbon chain glycols. values were negative at all temperatures for all glycol concentrations indicating the micellisation process is energetically favourable. Enthalpy–entropy compensation plots gave fairly constant compensation temperature values (≈300 K) for all the systems while compensation enthalpy values were less negative as the glycol concentration increased.

An Energetic Analysis of the Phase Separation in Non-Ionic Surfactant Mixtures: The Role of the Headgroup Structure

The main goal of this paper was to examine the effect of the hydrophilic surfactant headgroup on the phase behavior of non-ionic surfactant mixtures. Four mixed systems composed of an ethoxylated plus sugar-based surfactants, each having the same hydrophobic tail, were investigated. We found that the hydrophilicity of the surfactant inhibits the tendency of the system to phase separate, which is sensitive to the presence of NaCl. Applying a classical phase separation thermodynamic model, the corresponding energy parameters were evaluated. In all cases, the parameters were found to depend on the type of nonionic surfactant, its concentration in the micellar solution and the presence of NaCl in the medium. The experimental results can be explained by assuming the phase separation process takes place as a result of reduced hydration of the surfactant headgroup caused by a temperature increase. The enthalpy-entropy compensation plot exhibits excellent linearity. We found that all the mixed surfactant systems coincided on the same straight line, the compensation temperature being lower in the presence of NaCl.

Extrathermodynamic relations in the binding of charged and neutral substrates to sulfobutylether-β-CDs (SBE-β-CDs) and a 2-hydroxypropyl-β-CD (HP-β-CD)

The thermodynamics of binding of various neutral, cationic and anionic substrates to β-cyclodextrin, a hydroxylpropyl-β-cyclodextrin (HP4M-β-CD) and three sulfobutyl-β-cyclodextrins with varying degrees of total substitution (SBE1M-β-CD, SBE7M-β-CD, and SBE12M-β-CD) were determined by estimating binding constants, using a UV spectrophotometric technique, and temperature variation. linear free energy relation (LFER) plots and enthalpy–entropy Compensation (EEC) plots provided insight into the mechanisms of complexation as did carbon T1 relaxation times using NMR. LFER plots for charged molecules with HP4M-β-CD deviate from the neutral substrates suggesting differences in interaction modes. LFER plots for SBE7M-β-CD show that cationic substrates surprisingly fall within the same linear relationship for neutral substrates while anionic substrates deviate. The EEC plots for HP4M-β-CD show the largest loss of motion and degree of desolvation upon complexation. The interaction with SBE1M-β-CD was similar to that for β-CD. SBE7M-β-CD, and SBE12M-β-CD EEC plots are similar with the least loss of motion upon complex formation, suggesting a more organized and less flexible structure. This is supported by the T1 relaxation times for SBE1M-β-CD, SBE7M-β-CD, and SBE12M-β-CD, which show a critical distance at which the mobility of the side chain is reduced to form an extended cavity. No such evidence was seen with HP4M-β-CD, although the effect of varying of hydroxypropyl substitution was not studied.

A kinetic and thermodynamic study of the α-cyclodextrin mediated reaction of a range of p-substituted phenyl methyl sulfides with binding and non-binding peroxyacids

This paper presents a thermodynamic study of the rate and equilibria processes involved in the α-cyclodextrin mediated reaction of a range of 4-substituted phenyl methyl sulfides with two peroxyacids of different binding affinities. The results for the inclusion processes show that the formation of 1:1 and 2:1 (host:guest) complexes between α-cyclodextrin and phenyl methyl sulfides are generally enthalpically controlled, particularly so for the 2:1 complexes, as might be expected for a ternary complex. The data from this series of sulfides is presented as enthalpy-entropy compensation plots, yielding slopes of unity for each inclusion process. The formation of a 1:1 complex between cyclodextrin and the strongly associating 3-chloroperbenzoic acid (MCPBA) is also enthapically controlled. The other peroxyacid used, peroxomonosulfate, does not bind to α-cyclodextrin to any measurable degree. As described in our original study of this reaction system (Davies and Deary in J Chem Soc Perkin Trans 2:2423–2430, 1996), catalysis by α-cyclodextrin is effected by activation of the peroxide as a result its inclusion within the cyclodextrin cavity; hence for reactions of phenyl methyl sulfides with MCPBA, catalysis is observed, but is absent for PMS. In this study the reaction rates are analysed using the transition state pseudo-equilibrium approach of Tee (Carbohydr Res 192:181–195, 1989), whereby the transition state pseudoequilibrium constant K TS reflects the stabilisation imparted to the transition state by the association with one molecule of cyclodextrin. Enthalpy- entropy compensation plots for K TS give slopes close to unity; this is the first reported example of such plots being applied to transition state pseudoequilibrium constants.

U‐Shaped Conformation of Alkyl Chains Bound to a Synthetic Receptor Cucurbit[8]uril

The behavior of a series of alkanes bound to the molecular host cucurbit[8]uril (CB[8]) has been systematically studied by 2D (1)H NMR spectroscopy and isothermal titration calorimetry (ITC). CB[8] and alkyltrimethylammonium (C(m) TA(+), (CH(3))(3)N(+)C(m)H(2m+1), m=6-16) form 1:1 host-guest complexes with a high binding constant (K≈10(6) m(-1)). The shortest hexyl chain of C(6)TA(+) can be fully encapsulated in an extended conformation inside the CB[8] cavity, which is driven by both enthalpy and entropy. However, for the longer aliphatic chains, C(8)-C(16), the long alkyl tails take a U-shaped conformation inside the cavity, and their complexation is dominantly or almost exclusively enthalpy-driven, owing to the increased van der Waals contact between the folded aliphatic chain and the inner wall of the host cavity. As the chain length increases from C(8) to C(16), the ammonium head group of the guests moves away from the portal of CB[8] while the long aliphatic tails maintain the U-shaped conformation inside the cavity. The complexation of C(m)TA(+) with CB[8] follows the enthalpy-entropy compensation rule commonly observed in molecular recognition systems. For example, among the guest molecules, C(12)TA(+) shows the highest enthalpic gain (most favorable), owing to the large van der Waals contact between the guest and the host cavity, and at the same time the most unfavorable entropic contribution, owing to the severe conformational restriction of the U-shaped alkyl chain inside the host. The enthalpy-entropy compensation plot for the complexation suggests large conformational changes of the long alkyl chains and extensive dehydration associated with the inclusion complex formation.

Using Teicoplanin Based Chiral Stationary Phase to Explore Temperature Effects on Enantioseparation and Determination of Chiral Sulfoxides in Rat Serum

The methylated-teicoplanin aglycone chiral stationary phase (CSP) was used for the study of the enantioseparation and temperature behaviour of a set of chiral sulfoxides (nine different aryl methyl sulfoxides, 1-(methylsulfinyl) naphthalene and [(1,1-dimethyl-2-phenylethyl)sulfinyl]benzene) in polar organic mode. The effect of temperature on the HPLC separation of aromatic sulfoxides was studied between 10 and 50°C in methanol mobile phases with different concentration of organic modifier in mobile phase composition. The van't Hoff plots were constructed and thermodynamic data were determined from the slope and the intercept of linear van't Hoff plots for all 12 racemic compounds under the study. The van't Hoff plots (ln k versus 1/T and ln α versus 1/T) were linear for all enantiomers. The elution order (S (+) enantiomeric form eluted first) did not reverse in the temperature range of this study. Enthalpy-entropy compensation plots of ΔH i vs.ΔS i showed no significant linear correlation in methanol mobile phases used in this study. According to the enthalpy-entropy compensation plots of enantioselectivity, there is some significant linear correlation if the set of studied compounds is divided into two major groups. In order to observe the influence of temperature on retention and separation in biological matrix (rat serum), the solid phase extraction step was performed. The limit of determination (LOQ) was calculated for all studied compounds in the methanol mobile phase containing acetic acid (17.48 mmol/L) and diethylamine (4,79 mmol/L). The LOQ values were in the range of 7.0–24.2 ng/mL for racemic mixtures taking into consideration the recovery (82–96%) of the extraction procedure.

Isothermal Titration Calorimetry Reveals Differential Binding Thermodynamics of Variable Region-identical Antibodies Differing in Constant Region for a Univalent Ligand

The classical view of immunoglobulin molecules posits two functional domains defined by the variable (V) and constant (C) regions, which are responsible for antigen binding and antibody effector functions, respectively. These two domains are thought to function independently. However, several lines of evidence strongly suggest that C region domains can affect the specificity and affinity of an antibody for its antigen (Ag), independent of avidity-type effects. In this study, we used isothermal titration calorimetry to investigate the thermodynamic properties of the interactions of four V region-identical monoclonal antibodies with a univalent peptide antigen. Comparison of the binding of IgG1, IgG2a, IgG2b, and IgG3 with a 12-mer peptide mimetic of Cryptococcus neoformans polysaccharide revealed a stoichiometry of 1.9-2.0 with significant differences in thermodynamic binding parameters. Binding of this peptide to the antibodies was dominated by favorable entropy. The interaction of these antibodies with biotinylated peptides manifested greater enthalpy than for native peptides indicating that biotin labeling affected the types of Ag-Ab complexes formed. Our results provide unambiguous thermodynamic evidence for the notion that the C region can affect the interaction of the V region with an Ag.

Supramolecular Enantiodifferentiating Photocyclodimerization of 2-Anthracenecarboxylate Mediated by Capped γ-Cyclodextrins: Critical Control of Enantioselectivity by Cap Rigidity

A series of gamma-cyclodextrins (CDs) modified with capping and noncapping aromatic group(s) were synthesized to mediate the enantiodifferentiating [4 + 4] photocyclodimerization of 2-anthracenecarboxylic acid (AC). The complexation behavior of these gamma-CDs with AC was studied by circular dichroism, UV-vis, and NMR spectroscopy to reveal the formation of stable 1:2 host-guest complexes in all cases. The capped gamma-CD with a biphenyl group bridging the A and D glucose units was shown to confine the included AC molecules most strictly among the capped and noncapped gamma-CDs examined. Photocyclodimerization of AC mediated by capped gamma-CDs considerably improved the yield and enantiomeric excess (ee) of the head-to-head photodimer 3. The ee and the absolute configuration of syn-head-to-tail photodimer 2 critically depended on the rigidity of capping. Thus, the flexibly capped and rim-substituted gamma-CDs afforded 2 in moderate ee's of around 40%, whereas gamma-CD with a rigid biphenyl cap gave the antipodal 2 in -58% ee. Interestingly, the ee of 2 mediated by flexibly capped gamma-CDs was highly sensitive to the temperature variation as a consequence of large differential entropy changes in the enantiodifferentiation process. In contrast, the entropy effect does not appear to play a significant role in the photocyclodimerization of AC with rigidly capped gamma-CDs. The differential enthalpy and entropy changes obtained for the enantiodifferentiating photocyclodimerization mediated by native and most of the modified gamma-CDs gave an excellent enthalpy-entropy compensation plot with an exception of the biphenyl-capped gamma-CD, indicating the operation of significantly different enantiodifferentiation mechanism within the rigidly capped cyclodextrin cavity.

Retention behavior of ginsenosides on a poly(vinyl alcohol)-bonded stationary phase in hydrophilic interaction chromatography

The influences of the organic component of the mobile phase and the column temperature on the retention of ginsenosides on a poly(vinyl alcohol) (PVA) bonded stationary phase operated under hydrophilic interaction chromatographic mode were investigated. The retention of the ginsenosides was found to increase with increasing amount of acetonitrile (MeCN) in the mobile phase, which is typical of hydrophilic interaction chromatographic behavior. It was also found that the retention of the analytes was highly affected by the type of the organic modifier used. Aqueous MeCN (75-90%) gave the most satisfactory retention and separation of ginsenosides Rf, Rg1, Rd, Re, Rc, Rb2 and Rb1 compared with aqueous methanol, isopropyl alcohol or tetrahydrofuran at the same composition levels. The effects of the different types of organic modifiers on the retention of the analytes were attributed to their solvent strength and hydrogen-bond accepting/donating properties. The effect of temperature on the retention of ginsenoside on the PVA-bonded phase was assessed by constructing van't Hoff plots for two temperature ranges: subambient (273-293 K) and ambient-elevated (298-333 K) temperatures. van't Hoff plots for all analytes were linear at the two temperature intervals; however, the slopes of the lines corresponding to ginsenosides Rg1 and Re were completely different from those for the rest of the analytes especially in the subambient temperature range. Enthalpy-entropy compensation (EEC) studies were conducted to verify the difference in thermodynamics observed for ginsenosides Rg1 and Re compared with the other analytes. EEC plots showed that Rf, Rd, Rc, Rb2 and Rb1 were possibly retained by the same retention mechanism, which was completely different from that of Rg1 and Re at subambient temperatures. Retention prediction models were derived using multiple linear regression to identify solute attributes that affected the retention of the analytes on the PVA-bonded phase. The mathematical models derived revealed that the number of hydrogen-bond donors and the ovality of the molecules are important molecular properties that govern the retention of the compounds on the chromatographic system.

Elucidating the binding thermodynamics of 8‐anilino‐1‐naphthalene sulfonic acid with the A‐state of α‐lactalbumin: An isothermal titration calorimetric investigation

Isothermal titration calorimetry has been used to demonstrate that the heat profile associated with the binding of 8-anilino-1-naphthalene sulfonic acid (ANS) with the acid induced molten globule state (A-state) of alpha-lactalbumin (alpha-LA) is different from that with the native and denatured states of the protein. The results corroborate the spectroscopic observations that ANS binds more strongly to the partially folded states of the protein compared to that with the native and denatured states. ANS binds to the A-state of alpha-LA at two independent binding sites that remain nearly the same in the temperature range of 10-35 degrees C. The number of moles of ANS binding at site 1 at 10 degrees C is 14.0+/-0.2 and remains nearly the same with rise in temperature. However, the number of moles of ANS molecules binding at site 2 show an increase from 1.6+/-0.2 at 10 degrees C to 4.1+/-0.1 at 35 degrees C. The deviation of the slope of enthalpy-entropy compensation plot from unity and nonadherence to van't Hoff dictates implies that the binding sites on the A-state of alpha-LA for ANS are not well defined and specific; rather, these binding sites are formed due to greater exposure of hydrophobic clusters in the A-state of the protein. The results for the first time demonstrate the use of isothermal titration calorimetry in characterizing the A-state of alpha-LA both qualitatively and quantitatively.

Thermodynamic study of N-trifluoroacetyl-O-alkyl nipecotic acid ester enantiomers on diluted permethylated β-cyclodextrin stationary phase

Thermodynamic studies were performed on 12 pairs of N-trifluoroacetyl-O-alkyl nipecotic acid ester enantiomers on diluted permethylated beta-cyclodextrin stationary phase (CP Chirasil-Dex CB). The influence of ester alkyl group structure on interaction with permethylated beta-cyclodextrin (Me-CD) and enantioselectivity was studied. The types of alkyl groups studied included n-alkyl (C1-C5) and groups containing branching at differing locations relative to the chiral center of the molecule. The results show that for a given molecular weight, the n-alkyl esters have stronger interactions with Me-CD than esters containing branched alkyl groups. However, although having weaker interactions with Me-CD, esters containing alpha-branched alkyl groups exhibit higher enantioselectivity than the corresponding n-alkyl or beta-branched isobutyl esters. From the retention data, thermodynamic parameters were estimated using the retention increment method and enthalpy-entropy compensation plots (ln R' versus deltaH) were constructed. The results suggest that ester enantiomers with branching at the alpha-carbon of the ester alkyl group have additional and/or different types of enantioselective interactions with Me-CD than the C1-C5 n-alkyl esters or beta-branched isobutyl ester. In order to obtain a qualitative sense of the interaction with Me-CD, structures of the diastereomeric complexes formed between Me-CD and some of the ester enantiomers were modeled using simulated annealing molecular dynamics.

Study of the mechanism of enantioseparation part VI: thermodynamic study of HPLC separation of some enantiomers of phenylcarbamic acid derivatives on a (S,S) Whelk-O 1 column.

The enantiomers of thirteen 2-, 3-, and 4-alkoxyphenylcarbamic acid 2-methoxy-1-[(4-methylpiperazino)methyl]ethyl ester were separated on a (S,S) Whelk-O 1 CSP column isothermally in the range of 0-50 degrees C at 10 degrees C increments, using methanol/ water (90/10, v/v) containing 17.5 mmol L(-1) acetic acid and 14.36 mmol L(-1) triethylamine as a mobile phase. The dependence of the natural logarithms of retention and selectivity factors (In k, In alpha, respectively) on the inverse of temperature, 1/T, was used to determine thermodynamic data of enantiomers of alkoxysubstituted phenylcarbamic acid 2-methoxy-1-[(4-methylpiperazino) methyl]ethyl esters. Enthalpyentropy compensation plots showed that all of the compounds in this study separate via the same enthalpy-driven chiral recognition mechanism.

Study of the Mechanism of Enantioseparation. IX. Effect of Temperature on Retention of Chiral Compounds on a Methylated Teicoplanin Chiral Stationary Phase

The isocratic retention of enantiomers of chiral analytes (1‐methyl‐2‐piperidinoethylesters of 2‐, 3‐, and 4‐alkoxyphenylcarbamic acid, potential local anaesthetic drugs) was studied on a methylated teicoplanin CSP, at different temperatures (in the range of 0–50°C with 10°C increments) in the polar organic mode (the mobile phase composition consisted of methanol with 17.5 mmol/L acetic acid and 4.8 mmol/L diethylamine). The natural logarithms of the retention factors (ln k i ) of the investigated chiral compounds depended linearly on the inverse of temperature (1/T). van't Hoff plots afforded thermodynamic parameters, such as the apparent change in enthalpy (ΔH i ), the apparent change in entropy (ΔS i ), and the apparent change in Gibbs free energy (ΔG i ) for the transfer of analyte between the mobile phase and the stationary phase. The thermodynamic parameters were calculated in order to promote an understanding of the thermodynamic driving forces for retention in this chromatographic system. Enthalpy–entropy compensation plots showed that all of the compounds in this study separate via the same enthalpy driven chiral recognition mechanism.