An analytic potential energy function for the amide–amide and amide–water intermolecular hydrogen bonds in peptides

An analytic potential energy function is proposed and applied to evaluate the amide–amide and amide–water hydrogen‐bonding interaction energies in peptides. The parameters in the analytic function are derived from fitting to the potential energy curves of 10 hydrogen‐bonded training dimers. The analytic potential energy function is then employed to calculate the N? H…O?C, C? H…O?C, N? H…OH₂, and C?O…HOH hydrogen‐bonding interaction energies in amide–amide and amide–water dimers containing N‐methylacetamide, acetamide, glycine dipeptide, alanine dipeptide, N‐methylformamide, N‐methylpropanamide, N‐ethylacetamide and/or water molecules. The potential energy curves of these systems are therefore obtained, including the equilibrium hydrogen bond distances R(O…H) and the hydrogen‐bonding energies. The function is also applied to calculate the binding energies in models of β‐sheets. The calculation results show that the potential energy curves obtained from the analytic function are in good agreement with those obtained from MP2/6‐31+G** calculations by including the BSSE correction, which demonstrate that the analytic function proposed in this work can be used to predict the hydrogen‐bonding interaction energies in peptides quickly and accurately. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009     

Effects of benzoyl group substituents on the mesomorphic properties of 5-alkoxy-2-benzoylaminotropones

Three types of 5-alkoxy-2-benzoylaminotropones, containing an electron-donating group and seven types of derivatives with electron-withdrawing groups on the benzoyl group, were prepared in order to study the thermal ranges of the mesophases exhibited. The troponoid amides had higher transition temperatures than the corresponding troponoid esters and benzenoid amides. From the ¹H NMR spectroscopic measurements and X-ray crystallographic analysis of 5-butoxy-2-(4-methoxybenzoylamino)tropone, it was observed that the benzoyl carbonyl group faced to the H-3 of the tropone ring to form an intramolecular hydrogen bond between the tropone carbonyl and the amide NH groups. The intramolecular hydrogen bonding of the troponoid amides made the molecules flat, inducing strong π-π intermolecular interactions between head-to-tail dimers and so reduced the possibility of intermolecular hydrogen bonding between the NH group and the carbonyl group of neighbouring molecules so decreasing melting points. Electron-donating groups enhanced the appearance of nematic phases while electron-withdrawing groups promoted smectic A phases.     

Thermochemical Study of Solvation of Aliphatic Carboxamides in Aqueous Formamide Solutions

The entahlpies of solution of formamide, acetamide, and propionamide in aqueous formamide solutions (formamide concentration 8 mol kg^-1) at 298.15 K were measured. The entahlpies of transfer of amides from water to the mixed aqueous-organic solvent were calculated and compared with published data on the enthalpies of transfer of amides into aqueous urea solutions. The opposite trend in variation of the enthalpies of transfer of amides in these systems with increasing concentration of the nonaqueous component is due to different proton-donor power of formamide and urea relative to water. The enthalpy coefficients of pair interaction of amides with formamide in ternary aqueous solutions were calculated. Their positive values are due to endothermic interaction with formamide of the alkyl groups of amide molecules. The relative hydrophobicity of amides with different degrees of substitution of the amide group was estimated.     

Effects of benzoyl group substituents on the mesomorphic properties of 5-alkoxy-2-benzoylaminotropones

Three types of 5-alkoxy-2-benzoylaminotropones, containing an electron-donating group and seven types of derivatives with electron-withdrawing groups on the benzoyl group, were prepared in order to study the thermal ranges of the mesophases exhibited. The troponoid amides had higher transition temperatures than the corresponding troponoid esters and benzenoid amides. From the ¹H NMR spectroscopic measurements and X-ray crystallographic analysis of 5-butoxy-2-(4-methoxybenzoylamino)tropone, it was observed that the benzoyl carbonyl group faced to the H-3 of the tropone ring to form an intramolecular hydrogen bond between the tropone carbonyl and the amide NH groups. The intramolecular hydrogen bonding of the troponoid amides made the molecules flat, inducing strong π–π intermolecular interactions between head-to-tail dimers and so reduced the possibility of intermolecular hydrogen bonding between the NH group and the carbonyl group of neighbouring molecules so decreasing melting points. Electron-donating groups enhanced the appearance of nematic phases while electron-withdrawing groups promoted smectic A phases.     

Intramolecular hydrogen bonds with large proton polarizability in semisalts of mono- and di-N-oxides of N,N′-tetraalkyl-o-xylyldiamines

Heteroconjugated NO⁺H … N NO … H⁺N and homoconjugated NO⁺H … ON NO … H⁺ON intramolecular hydrogen bonds formed in semisalts of mono- and di-N-oxides of N,N′-tetraalkyl-o-xylyldiamines were studied by IR and NMR spectroscopy. All these hydrogen bonds show large proton polarizability. In the case of the heteroconjugated hydrogen bonds the proton transfer equilibrium shifts from compounds 1 to 3 to the left hand side since the interaction of the hydrogen bond with the solvent environment decreases in this series of compounds. With compound 1 the hydrogen bonds are slightly weaker and longer, hence the wavenumber dependence of the intensity of the continuum caused by these hydrogen bonds is slightly changed with compound 1 compared with compound 2. In the case of compound 3 the intensity of the continuum decreases because of increasing screening of the hydrogen bonds. In the series of homoconjugated hydrogen bonds, from compound 4 to 6 the intense continuum vanishes, and only the band of the 0–1 proton transition at 950 cm⁻¹ remains. The vanishing of the continuum is caused by increasing screening of the hydrogen bonds against their solvent environments by bulky groups, and thus, this change demonstrates again that the interaction of the hydrogen bond with large proton polarizabilities is a necessary prerequisite for IR continua to appear.     

AM1 studies of hydrogen bonded adducts between 2,5-dihydroxy-p-quinone and N-bases

Semiempirical AM1 calculations were used to optimize the geometry of the adducts formed by 2,5-dihydroxy-p quinone (DHpQ) with substituted pyridines or imidazole. Hydrogen bond formation was seen to be responsible for the stability of the adducts. From the study of the total energy function, obtained by imposing fixed positions to the proton, two structures were found to be possible for each adduct, one schematically indicated as -OH … N-base and the proton transfer one, indicated as -O⁻ … HN⁺base. The proton transfer energy was found to vary linearly with the base pK_a value. A study was also carried out on the system formed by DHpQ and a cluster of three water molecules acting as proton acceptors. The implications were discussed relating to possible hydrogen bond formation between trihydroxyphenylalanine quinone, the coenzyme of bovine serum amine oxidase, and some basic residue or water molecule, lying close to the protein active site.     

The crystal structures at 80 K and IR spectra of the complex of 4-methylpyridine with pentachlorophenol and its deuterated analogue

The crystal structures of the complex of 4-methylpyridine with pentachlorophenol (MP-PCP) and its deuterated analogue (MP-PCP-d) were determined at 80 K by X-ray diffraction. The MP-PCP complex crystallizes in the space group P with a = 7.267(7), b = 8.966(9), c = 13.110(14)Å, = 99.70(8), β = 118.16(9), γ = 103.38(8)° and Z = 2 and the MP-PCP-d complex in the monoclinic Cc space group with a = 3.826(2), b = 27.54(2), c = 13.209(12)Å, β = 101.38(9)° and Z = 4. The O… H … N bridge bond distance of 2.515(4) Å is significantly shorter than that determined at room temperature (2.552(4) Å) and the O---D … N bond length of 2.628(6) Å is only slightly shorter than at room temperature (2.638(3) Å). The temperature dependence of the IR spectra confirms the symmetrization of the OHN hydrogen bond.     

Amide-Amide and Amide-Water Hydrogen Bonds: Implications for Protein Folding and Stability

Amide-amide hydrogen bonds have been implicated in directing protein folding and enhancing protein stability. Inversion transfer (13)C NMR spectroscopy and IR spectroscopy were used to compare the ability of various amide solvents and of water to alter the rate of the cis-trans isomerization of the prolyl peptide bond of Ac-Gly-[β,δ-(13)C]Pro-OMe and the amide I vibrational mode of [(13)C=O]Ac-Pro-OMe. The results indicate that secondary amides are significantly weaker hydrogen bond donors than is formamide or water. These results are most consistent with models for protein folding in which the formation of secondary structure is a cooperative process that follows hydrophobic collapse. These results also suggest that a hydrogen bond between a main-chain oxygen and an asparagine or glutamine sidechain may contribute more to protein stability than does a main-chain-main-chain hydrogen bond.     

Key Role of Intramolecular Metal Chelation and Hydrogen Bonding in the Cobalt‐Mediated Radical Polymerization of N‐Vinyl Amides

This work reveals the preponderance of an intramolecular metal chelation phenomenon in a controlled radical polymerization system involving the reversible trapping of the radical chains by a cobalt complex bis(acetylacetonato)cobalt(II). The cobalt‐mediated radical polymerization (CMRP) of a series of N‐vinyl amides was considered with the aim of studying the effect of the cobalt chelation by the amide moiety of the last monomer unit of the chain. The latter reinforces the cobalt? polymer bond in the order N‐vinylpyrrolidone<N‐vinyl caprolactam<N‐methyl‐N‐vinyl acetamide, and is responsible for the optimal control of the polymerizations observed for the last two monomers. Such a double linkage between the controlling agent and the polymer, through a covalent bond and a dative bond, is unique in the field of controlled radical polymerization and represents a powerful opportunity to fine tune the equilibrium between latent and free radicals. Possible hydrogen bond formation is also taken into account in the case of N‐vinyl acetamide and N‐vinyl formamide. These results are essential for understanding the factors influencing Co? C bond strength in general, and the CMRP mechanism in particular, but also for developing a powerful platform for the synthesis of new precision poly(N‐vinyl amide) materials, which are an important class of polymers that sustain numerous applications today.     

Electrostatic DFT map for the complete vibrational amide band of NMA

An anharmonic vibrational Hamiltonian for the amide I, II, III, and A modes of N-methyl acetamide (NMA), recast in terms of the 19 components of an external electric field and its first and second derivative tensors (electrostatic DFT map), is calculated at the DFT(BPW91/6-31G(d,p)) level. Strong correlations are found between NMA geometry and the amide frequency fluctuations calculated using this Hamiltonian together with the fluctuating solvent electric field obtained from the MD simulations in TIP3 water. The amide I and A frequencies are strongly positively correlated with the C=O and N-H bond lengths. The C=O and C-N amide bond lengths are negatively correlated, suggesting the solvent-induced fluctuations of the contribution of zwitterionic resonance form. Sampling the global electric field in the entire region of the transition charge densities (TCDs) is required for accurate infrared line shape simulations. Collective electrostatic solvent coordinates which represent the fluctuations of the 10 lowest amide fundamental and overtone states are reported. Normal-mode analysis of an NMA-3H(2)O cluster shows that the 660 cm(-1) to 1100 cm(-1) oscillation found in the frequency autocorrelation functions of the amide modes may be ascribed to the two bending vibrations of intermolecular hydrogen bonds with the amide oxygen of NMA.     

The effect of intermolecular hydrogen bonding on the planarity of amides

Ab initio and density functional theory (DFT) calculations on some model systems are presented to assess the extent to which intermolecular hydrogen bonding can affect the planarity of amide groups. Formamide and urea are examined as archetypes of planar and non-planar amides, respectively. DFT optimisations suggest that appropriately disposed hydrogen-bond donor or acceptor molecules can induce non-planarity in formamide, with OCNH dihedral angles deviating by up to ca. 20° from planarity. Ab initio energy calculations demonstrate that the energy required to deform an amide molecule from the preferred geometry of the isolated molecule is more than compensated by the stabilisation due to hydrogen bonding. Similarly, the NH(2) group in urea can be made effectively planar by the presence of appropriately positioned hydrogen-bond acceptors, whereas hydrogen-bond donors increase the non-planarity of the NH(2) group. Small clusters (a dimer, two trimers and a pentamer) extracted from the crystal structure of urea indicate that the crystal field acts to force planarity of the urea molecule; however, the interaction with nearest neighbours alone is insufficient to induce the molecule to become completely planar, and longer-range effects are required. Finally, the potential for intermolecular hydrogen bonding to induce non-planarity in a model of a peptide is explored. Inter alia, the insights obtained in the present work on the extent to which the geometry of amide groups may be deformed under the influence of intermolecular hydrogen bonding provide structural guidelines that can assist the interpretation of the geometries of such groups in structure determination from powder X-ray diffraction data.     

Microsolvation of formamide: a rotational study

Microsolvated formamide clusters have been generated in a supersonic jet expansion and characterized using Fourier transform microwave spectroscopy. Three conformers of the monohydrated cluster and one of the dihydrated complex have been observed. Seven monosubstituted isotopic species have been measured for the most stable conformer of formamide...H(2)O, which adopts a closed planar ring structure stabilized by two intermolecular hydrogen bonds (N-H...O(H)-H...O=C). The two higher energy forms of formamide...H(2)O have been observed for the first time. The second most stable conformer is stabilized by a O-H...O=C and a weak C-H...O hydrogen bond, while, in the less stable form, water accepts a hydrogen bond from the anti hydrogen of the amino group. For formamide...(H(2)O)(2), the parent and nine monosubstituted isotopic species have been observed. In this cluster the two water molecules close a cycle with the amide group through three intermolecular hydrogen bonds (N-H...O(H)-H...O(H)-H...O=C), the nonbonded hydrogen atoms of water adopting an up-down configuration. Substitution (r(s)) and effective (r(0)) structures have been determined for formamide, the most stable form of formamide...H(2)O and formamide...(H(2)O)(2). The results on monohydrated formamide clusters can help to explain the observed preferences of bound water in proteins. Clear evidence of sigma-bond cooperativity effects emerges when comparing the structures of the mono- and dihydrated formamide clusters. No detectable structural changes due to pi-bond cooperativity are observed on formamide upon hydration.     

A scheme for rapid prediction of cooperativity in hydrogen bond chains of formamides,acetamides, and N‐methylformamides

A scheme is proposed in this article to predict the cooperativity in hydrogen bond chains of formamides, acetamides, and N‐methylformamides. The parameters needed in the scheme are derived from fitting to the hydrogen bonding energies of MP2/6‐31+G** with basis set superposition error (BSSE) correction of the hydrogen bond chains of formamides containing from two to eight monomeric units. The scheme is then used to calculate the individual hydrogen bonding energies in the chains of formamides containing 9 and 12 monomeric units, in the chains of acetamides containing from two to seven monomeric units, in the chains of N‐methylformamides containing from two to seven monomeric units. The calculation results show that the cooperativity predicted by the scheme proposed in this paper is in good agreement with those obtained from MP2/6‐31+G** calculations by including the BSSE correction, demonstrating that the scheme proposed in this article is reasonable. Based on our scheme, a cooperativity effect of almost 240% of the dimer hydrogen bonding energy in long hydrogen bond formamide chains, a cooperativity effect of almost 190% of the dimer hydrogen bonding energy in long hydrogen bond acetamide chains, and a cooperativity effect of almost 210% of the dimer hydrogen bonding energy in long hydrogen bond N‐methylformamide chains are predicted. The scheme is further applied to some heterogeneous chains containing formamide, acetamide, and N‐methylformamide. The individual hydrogen bonding energies in these heterogeneous chains predicted by our scheme are also in good agreement with those obtained from Møller‐Plesset calculations including BSSE correction. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010     

Ab initio studies of structural features not easily amenable to experiment: Part 6. Quantitative estimate of the effect of bond delocalization on structure and hyperconjugative interaction of the amide group

The structural changes, which occur in the amide unit when the NH₂-group is twisted out of plane by rotation about the NC bond, have been determined by comparing the completely relaxed ab initio geometries of planar and perpendicular formamide and acetamide. In the perpendicular conformation, in which the π-electron amide resonance is uncoupled, the NC bond distance is 0.080.09 Å longer than in the planar form; the CO bond distance is about 0.01 Å shorter; NH distances are about 0.01 Å longer; and HNC angles are 510° smaller, whereas the CNO angle is relatively constant. Because of the apparent invariance of CH₃-hyperconjugation effects in planar and perpendicular acetamide, it is tentatively postulated that anomeric orbital interactive effects (involving the lone pair on NH, the CO π-electron pair and antibonding π*-group-orbitals on C(α) in NHC(HR)C(O)), which should be an important factor in determining peptide chain conformation, do not vary significantly with small deviations from amide group planarity.     

Solution structure, mutagenesis, and NH exchange studies of the MutT enzyme–Mg-8-oxo-dGMP complex

The MutT pyrophosphohydrolase from E. coli (129 residues) catalyzes the hydrolysis of nucleoside triphosphates (NTP), including 8-oxo-dGTP, by substitution at Pβ, to yield NMP and pyrophosphate. The product, 8-oxo-dGMP is an unusually tight binding, slowly exchanging inhibitor with a K_D=52 nM, (ΔG°=−9.8 kcal/mol) which is 6.1 kcal/mol tighter than the binding of dGMP (ΔG°=−3.7 kcal/mol). The higher affinity for 8-oxo-dGMP results from a more favorable ΔH_binding (−32 kcal/mol) despite an unfavorable −TΔS°_binding (+22 kcal/mol). The solution structure of the MutT–Mg²⁺-8-oxo-dGMP complex shows a narrowed, hydrophobic nucleotide-binding cleft with Asn-119 and Arg-78 among the few polar residues. The N119A, N119D, R78K and R78A single mutations, and the R78K+N119A double mutant all showed largely intact active sites, on the basis of small changes in the kinetic parameters of dGTP hydrolysis and in ¹H–¹⁵N HSQC spectra. However, the N119A mutation profoundly weakened the active site binding of 8-oxo-dGMP by 4.3 kcal/mol (1650-fold). The N119D mutation also weakened 8-oxo-dGMP binding but only by 2.1 kcal/mol (37-fold), suggesting that Asn-119 functioned both as a hydrogen bond donor to C8=O, and a hydrogen bond acceptor from N7H of 8-oxo-dGMP, while aspartate at position −119 functioned as an acceptor of a single hydrogen bond. Much smaller weakening effects (0.3–0.4 kcal/mol) on the binding of dGMP and dAMP were found, indicating specific hydrogen bonding of Asn-119 to 8-oxo-dGMP. While formation of the wild type MutT–Mg²⁺-8-oxo-dGMP complex slowed the backbone NH exchange rates of 45 residues distributed throughout the protein, the same complex of the N119A mutant slowed the exchange rates of only 11 residues at or near the active site, indicating an increase in conformational flexibility of the N119A mutant. The R78K and R78A mutations weakened the binding of 8-oxo-dGMP by 1.7 and 1.1 kcal/mol, respectively, indicating a lesser role of Arg-78 than of Asn-119 in the selective binding of 8-oxo-dGMP, likely donating a single hydrogen bond to its C6=O. The R78K+N119A double mutant weakened the binding of 8-oxo-dGMP (K_I^slope=3.1 mM) by 6.5±0.2 kcal/mol which overlaps, within error with the sum of the effects of the two single mutants (6.0±0.3 kcal/mol). Such additive effects of the two single mutants in the double mutant are most simply explained by the independent functioning of Asn-119 and Arg-78 in the binding of 8-oxo-dGMP. Independent functioning of these two residues in nucleotide binding is consistent with their locations in the MutT–Mg²⁺-8-oxo-dGMP complex, on opposite sides of the active site cleft, with a distance of 8.4±0.5 Å between their side chain nitrogens.     

Formation of hydrogen-bonded chains between a strong base with guanidine-like character and phenols with various pKa values - an FT-IR study

The complexes formed by phenols with 1,3,4,6,7,8-hexahydro-1-methyl-2H-pyrimido[1,2-a]pyrimidine (mTBD), an N-base with guanidine-like character, were studied as a function of the pK_a of the phenols by FT-IR spectroscopy. The following phenols were used: 4-cyanophenol (4-CNPh), pentachlorophenol (PCP) and 2,6-dichloro-4-nitrophenol (DNPh). In the case of chloroform solutions of 1:1 mixtures of the phenols with MTBD the corresponding complexes are formed completely. With increasing acidity of the phenols the hydrogen bonds become increasingly asymmetrical. The OH … N ⁻O … H⁺N hydrogen bond in the 4-CNPh-MTBD complex shows large proton polarizability. In the other cases only the polar structure is realized. With increasing phenol MTBD ratio, the formation of chains with two phenol molecules is observed. With decreasing pK_a of the phenols the fluctuation is limited to the phenol-phenolate bond and finally, the phenol-protonated MTBD bond begins to dissociate. In acetonitrile solutions, N⁺H … O⁻ hydrogen bonds are observed in the case of the 1:1 mixture of 4-CNPh with MTBD. A weak continuum indicates the presence of homoconjugated phenol-phenolate bonds with large proton polarizability. In the case of 2:1 mixtures only protonated MTBD and homoconjugated phenol-phenolate bonds are observed, independent of the pK_a of the phenols. The results are discussed with regard to the proton pathway in bacteriorhodopsin.     

Hydrogen-bonding dynamics in aqueous solutions of amides and acids: monomer, dimer, trimer, and polymer

Hydrogen-bonding dynamics in aqueous solutions of series of amides and acids have been investigated by means of femtosecond Raman-induced Kerr effect spectroscopy and ab initio quantum chemistry calculation. The amides and acids studied here are acetamide, 1,3-propanedicarboxamide, 1,3,5-pentanetricaroxamide, polyacrylamide with Mw=1500, acetic acid, 1,3-propanedicarboxylic acid, 1,3,5-pentanetricarboxylic acid, and poly(acrylic acid) with Mw=2000. The femtosecond damped transient feature for aqueous amide solutions, which arises from the intermolecular hydrogen bonds of amide and water, becomes clearer with the larger molecular weight of amide. A characteristic vibrational band at about 100 cm(-1) is assigned as the hydrogen-bonding vibrational mode and the ab initio quantum chemistry calculation result indicates that at least two waters, which make up the hydrogen-bonding network with amide, are necessary for this mode. The hydrogen-bonding vibrational mode at about 100 cm(-1) in aqueous amide solutions shifts to the higher frequency with the larger molecular weight amide in consequence of the stronger intermolecular interaction between amide and water. The evidence likely comes from the stronger hydrophobic interaction for polymer than oligomers and monomer. In the picosecond time region, an extra slow relaxation process with a time constant of about 60 ps has been found in the aqueous polymer solutions. The relaxation is assigned as a local motion of the constitutional repeat unit of polymers from comparison with monomer and oligomers.     

Enthalpies of solution of glycylglycine and diglycylglycine in aqueous alcohols at 298.15 K

The integral enthalpies of solution of glycylglycine and diglycylglycine in water–ethanol, water–n-propanol and water–i-propanol mixtures were measured at 298.15 K and alcohol mole fraction concentrations (x₂) ranging up to 0.3 by calorimetry. The Δ_solH° and Δ_trH° vs. x₂ were found to have extrema. Enthalpic coefficients of pairwise interactions (h_xy) between peptide and alcohol molecules were positive and increased in the series ethanol, n-propanol, i-propanol.     

The nature of the structure difference between light and heavy water and the origin of the solvent isotope effect—I

The observed differences in heat content, entropy and free energy of light and heavy liquid water can be calculated within experimental error from measured infrared frequencies, using a model for water with tetrahedral hydrogen bonding and treating the hindered rotations (librations) of the water molecules as three-dimensional isotropic harmonic oscillators. The origin of the solvent isotope effect for monatomic ions in light and heavy water is their effect on the structure difference between light and heavy water. The quantity Δθ = h Δν/k provides a measure of this structure difference, where Δν is ν−ν′, the difference in average values of the librational frequencies of H₂O and D₂O, and ν′=ν/1·3815. Differences in heat content, entropy and free energy for solution of monatomic ions in light and heavy water and individual ionic activity coefficients can be calculated from Δθ. Hydronium and hydroxide ions are also discussed.     

Crystalline calcium phenylphosphonate—thermodynamic data on n-alkylmonoamine intercalations

Lamellar crystalline calcium phenylphosphonate, as anhydrous Ca(HO₃PC₆H₅)₂ and hydrated Ca(HO₃PC₆H₅)₂·2H₂O compounds, were used as hosts for intercalation of polar n-alkylmonoamine molecules of the general formula CH₃(CH₂)_nNH₂ (n=0–4, 7) in water or 1,2-dichloroethane. An increase in the interlayer distance was observed. The exothermic enthalpic values for intercalation increased with the number of carbon atoms and with increasing concentration of the amines. The intercalation followed by a titration procedure in the solid/liquid interface with Ca(HO₃PC₆H₅)₂·2H₂O and Ca(HO₃PC₆H₅)₂ gave the enthalpy/number of carbons correlations: Δ_intH=−(1.74±0.43)–(1.30±0.13)n_c and Δ_intH=−(4.15±0.15)–(1.07±0.03)n_c, for water and 1,2-dichloroethane, respectively. A similar correlation Δ_intH=−(4.27±0.80)–(1.85±0.21)n_c was obtained in water by using the ampoule breaking procedure for Ca(HO₃PC₆H₅)₂·2H₂O. The increase in exothermic enthalpic values with the increase in n-aliphatic carbon atoms is more pronounced for the anhydrous compound and also when using the ampoule breaking procedure. The Gibbs free energies are negative. Positive entropic values favor intercalation in these systems.