Structure-property relationships in protic ionic liquids: a study of solvent-solvent and solvent-solute interactions.

The ionic nature of a functionalized protic ionic liquid cannot be rationalized simply through the differences in aqueous proton dissociation constants between the acid precursor and the conjugate acid of the base precursor. The extent of proton transfer, i.e. the equilibrium ionicity, of a tertiary ammonium acetate protic ionic liquid can be significantly increased by introducing an hydroxyl functional group on the cation, compared to the alkyl or amino-functionalized analogues. This increase in apparent ionic nature correlates well with variations in solvent-solute and solvent-solvent interaction parameters, as well as with physicochemical properties such as viscosity.

Structure-property relationships in protic ionic liquids: a thermochemical study.

How does cation functionality influence the strength of intermolecular interactions in protic ionic liquids (PILs)? Quantifying the energetics of PILs can be an invaluable tool to answer this fundamental question. With this in view, we have determined the standard molar enthalpy of vaporization, , and the standard molar enthalpy of formation, , of three tertiary ammonium acetate PILs with varying cation functionality, and of their corresponding precursor amines, through a combination of Calvet-drop microcalorimetry, solution calorimetry, and ab initio calculations. The obtained results suggest that these PILs vaporize as their neutral acid and base precursors. We also found a strong correlation between of the PILs and of their corresponding amines. This suggests that, within this series of PILs, the influence of cation modification on their cohesive energies follows a group additivity rule. Finally, no correlation between the of PILs and the extent of proton transfer, as estimated from the difference in aqueous pKa between the precursor acid and the conjugate acid of the precursor base, was observed.

Energetics of Radical Formation in Eumelanin Building Blocks: Implications for Understanding Photoprotection Mechanisms in Eumelanin.

The supramolecular structure of melanin pigments is characterized by a high concentration of radical species. Therefore, the energetics of the radical formation in melanin building blocks is key for understanding the structure and the electronic properties of the pigments at the molecular level. Nevertheless, the radical energetics of even the simplest melanin building blocks are largely unknown. In order to address this fundamental issue, the bond dissociation enthalpies (BDEs) for the melanin monomers 5,6-dihydroxy-1H-indole-2-carboxylic acid (DHICA), 1H-indole-5,6-diol (DHI), and 1H-indole-5,6-dione (IQ) were determined through high-accuracy ab initio quantum chemistry methods. Our results provide strong evidence of the importance on BDEs for explaining the experimentally observed dependence of the antioxidant properties of eumelanin pigments on the DHICA/DHI ratio, and the role that these two species play on the photoprotection mechanism.

The thermochemistry of cubane 50 years after its synthesis: a high-level theoretical study of cubane and its derivatives.

The gas-phase enthalpy of formation of cubane (603.4 ± 4 kJ mol(-1)) was calculated using an explicitly correlated composite method (W1-F12). The result obtained for cubane, together with the experimental value for the enthalpy of sublimation, 54.8 ± 2.0 kJ mol(-1), led to 548.6 ± 4.5 kJ mol(-1) for the solid-phase enthalpy of formation. This value is only 6.8 kJ mol(-1) higher than the 50-year-old original calorimetric result. The carbon-hydrogen bond dissociation enthalpy (C-H BDE) of cubane (438.4 ± 4 kJ mol(-1)), together with properties relevant for its experimental determination using gas-phase ion thermochemistry, namely the cubane gas-phase acidity (1704.6 ± 4 kJ mol(-1)), cubyl radical electron affinity (45.8 ± 4 kJ mol(-1)), cubane ionization energy (1435.1 ± 4 kJ mol(-1)), cubyl radical cation proton affinity (918.8 ± 4 kJ mol(-1)), cubane cation appearance energy (1099.6 ± 4 kJ mol(-1)), and cubyl ionization energy (661.2 ± 4 kJ mol(-1)), were also determined. These values were compared with those calculated for unstrained hydrocarbons (viz., methane, ethane, and isobutane). The strain energy of cubane (667.2 kJ mol(-1)) and cubyl radical (689.4 kJ mol(-1)) were independently estimated via quasihomodesmotic reactions. These values were related via a simple model to the C-H BDE in cubane. Taking into account the accuracy of the computational method, the comparison with high-precision experimental results, and the data consistency afforded by the relevant thermodynamic cycles, we claim an uncertainty better than ±4 kJ mol(-1) for the new enthalpy of formation values presented.

Enthalpy of formation of anisole: implications for the controversy on the O-H bond dissociation enthalpy in phenol.

Significant discrepancies in the literature data for the enthalpy of formation of gaseous anisole, ΔfHmo(PhOCH3, g), have fueled an ongoing controversy regarding the most reliable enthalpy of formation of the phenoxy radical and of the gas phase O-H bond dissociation enthalpy, DHo(PhO-H), in phenol. In the present work ΔfHmo(PhOCH3, g) was reassessed using a combination of calorimetric determinations and high-level (W2-F12) ab initio calculations. Static-bomb combustion calorimetry led to the standard molar enthalpy of formation of liquid anisole at 298.15 K, ΔfHmo(PhOCH3, l) = −(117.1 ± 1.4) kJ·mol(-1). The corresponding enthalpy of vaporization was obtained as, ΔvapHmo(PhOCH3) = 46.41 ± 0.26 kJ·mol(-1), by Calvet-drop microcalorimetry. These results give ΔfHmo(PhOCH3, g) = −(70.7 ± 1.4) kJ·mol(-1), in excellent agreement with ΔfHmo(PhOCH3, g) = −(70.8 ± 3.2) kJ·mol(-1), obtained from the W2-F12 calculations. The ΔfHmo(PhOCH3, g) here recommended leads to ΔfHmo(PhO•, g) = 55.5 ± 2.4 kJ·mol(-)1 and DH°(PhO-H) = 368.1 ± 2.6 kJ·mol(-1).

Energetics and structure of simvastatin.

The study of structure-energetics relationships for active pharmaceutical ingredients has received considerable attention in recent years, due to its importance for the effective production and safe use of drugs. In this work the widely prescribed cholesterol-lowering drug simvastatin was investigated by combining experimental (combustion calorimetry and differential scanning calorimetry, DSC) and computational chemistry (quantum chemistry and molecular dynamics calculations) results. The studies addressed the crystalline form stable at ambient temperature (form I) and the liquid and gaseous phases. Heat capacity determinations by DSC showed no evidence of polymorphism between 293 K and the fusion temperature. It was also found that the most stable molecular conformation in the gas phase given by the quantum chemistry calculations (B3LYP-D3/cc-pVTZ) is analogous to that observed in the crystal phase. The molecular dynamics simulations correctly captured the main structural properties of the crystalline phase known from published single crystal X-ray diffraction results (unit cell dimensions and volume). They also suggested that, while preferential conformations are exhibited by the molecule in the solid at 298.15 K, these preferences are essentially blurred upon melting. Finally, the experiments and calculations led to enthalpies of formation of simvastatin at 298.15 K, in the crystalline (form I) ΔfH(m)(o) (cr I) = -1238.4 ± 5.6 kJ · mol(-1), liquid ΔfH(m)(o) (l) = -1226.4 ± 5.7 kJ · mol(-1), and gaseous ΔfH(m)(o) (g) = -1063.0 ± 7.1 kJ · mol(-1) states.

Energetics of nonbonded ortho interactions in alkylbenzenes.

The gas-phase enthalpies of formation for a set of ortho-substituted alkylbenzenes were obtained from CCSD(T*)-F12 and W1-F12 calculations. Most values are in keeping with available experimental data. The gas-phase enthalpies of formation of 1-ethyl-2-propylbenzene, 1-ethyl-2-isopropylbenzene, 1,2-diisopropylbenzene, 1,2,4-triethylbenzene, and 1,2,4,5-tetraethylbenzene, for which no experimental data are available, were determined as -46.0, -46.8, -68.7, -76.9, and -116.8 kJ mol(-1), respectively (estimated error bar ±4 kJ mol(-1)). The whole set of experimental and theoretical values are in good agreement with the estimates obtained using the extended Laidler bond additivity (ELBA) method. This agreement supports the approximation used in ELBA that interactions between ortho alkyl groups (other than tertiary alkyl groups) have roughly the same magnitude as a methyl-methyl interaction.

Energetics of tert-butoxyl addition reaction to norbornadiene: a method for estimating the pi-bond strength of a carbon-carbon double bond.

The energetics of tert-butoxyl radical addition reaction to norbornadiene was investigated by time-resolved photoacoustic calorimetry (TR-PAC). The result, together with the C-O bond dissociation enthalpy (BDE) in the addition product, allowed us to calculate the pi-bond dissociation enthalpy in norbornadiene. Quantum chemistry (QC) methods were also used to obtain several enthalpies of reaction of the addition of oxygen-centered radicals to alkenes. The pi-bond dissociation enthalpies in these molecules were calculated by a procedure similar to that used in the case of norbornadiene and were compared with the pi-BDE values obtained by the method proposed by Benson. These two different approaches yield similar values for the pi-BDEs in alkenes, indicating that the addition method proposed in the present study is a valid way to derive that quantity. The influence of strain in the pi-BDEs of cyclic alkenes was investigated and allowed us to justify the difference between the pi-BDE in norbornene and norbornadiene. Finally, the thermochemistry of the addition and abstraction reactions involving these two molecules and tert-butoxyl radical was analyzed.

Energetic differences between the five- and six-membered ring hydrocarbons: strain energies in the parent and radical molecules.

The C-H bond dissociation enthalpies (BDEs) for the five- and six-membered ring alkanes, alkenes, and dienes were investigated and discussed in terms of conventional strain energies (SEs). New determinations are reported for cyclopentane and cyclohexane by time-resolved photoacoustic calorimetry and quantum chemistry methods. The C-H BDEs for the alkenes yielding the alkyl radicals cyclopenten-4-yl and cyclohexen-4-yl and the alpha-C-H BDE in cyclopentene were also calculated. The s-homodesmotic model was used to determine SEs for both the parent molecules and the radicals. When the appropriate s-homodesmotic model is chosen, the obtained SEs are in good agreement with the ones derived from group additivity schemes. The different BDEs in the title molecules are explained by the calculated SEs in the parent molecules and their radicals: (1) BDEs leading to alkyl radicals are ca. 10 kJ mol (-1) lower in cyclopentane and cyclopentene than in cyclohexane and cyclohexene, due to a smaller eclipsing strain in the five-membered radicals relative to the parent molecules (six-membered hydrocarbons and their radicals are essentially strain free). (2) C-H BDEs in cyclopentene and cyclohexene leading to the allyl radicals are similar because cyclopenten-3-yl has almost as much strain as its parent molecule, due to a synperiplanar configuration. (3) The C-H BDE in 1,3-cyclopentadiene is 27 kJ mol (-1) higher than in 1,4-cyclohexadiene due to the stabilizing effect of the conjugated double bond in 1,3-cyclopentadiene and not to a destabilization of the cyclopentadienyl radical. The chemical insight afforded by group additivity methods in choosing the correct model for SE estimation is highlighted.

Energetics of the allyl group.

Aiming to improve our understanding of the stability of radicals containing the allylic moiety, carbon-hydrogen bond dissociation enthalpies (BDEs) in propene, isobutene, 1-butene, (E)-2-butene, 3-metylbut-1-ene, (E)-2-pentene, (E)-1,3-pentadiene, 1,4-pentadiene, cyclohexene, 1,3-cyclohexadiene, and 1,4-cyclohexadiene have been determined by quantum chemistry calculations. The BDEs in cyclohexene, 1,3-cyclohexadiene, and 1,4-cyclohexadiene have also been obtained by time-resolved photoacoustic calorimetry. The theoretical study involved a DFT method as well as ab initio complete basis-set approaches, including the composite CBS-Q and CBS-QB3 procedures, and basis-set extrapolated coupled-cluster calculations (CCSD(T)). By taking the C(sp3)-H BDE in propene as a reference, we have concluded that one methyl group bonded to C3 in propene (i.e., 1-butene) leads to a decrease of 12 kJ mol(-1) and that a second methyl group bonded to C3 (3-methylbut-1-ene) further decreases the BDE by 8 kJ mol(-1). When the methyl group is bonded to C2 in propene (isobutene), an increase of 7 kJ mol(-1) is observed. Finally, a methyl group bonded to C1 in propene (2-butene) has essentially no effect (-1 kJ mol(-1)). While this trend can be rationalized in terms of stabilization of the corresponding radical (through hyperconjugation and pi-delocalization), the BDE values observed for the dienes can only be understood by considering the thermodynamic stabilities of the parent compounds.

Enthalpy of formation of the cyclopentadienyl radical: photoacoustic calorimetry and ab initio studies.

The gas-phase C-H bond dissociation enthalpy (BDE) in 1,3-cyclopentadiene has been determined by time-resolved photoacoustic calorimetry (TR-PAC) as 358 +/- 7 kJ mol(-1). Theoretical results from ab initio complete basis-set approaches, including the composite CBS-Q and CBS-QB3 procedures, and basis-set extrapolated coupled-cluster calculations (CCSD(T)) are reported. The CCSD(T) prediction for the C-H BDE of 1,3-cyclopentadiene (353.3 kJ mol(-1)) is in good agreement with the TR-PAC result. On the basis of the experimental and the theoretical values obtained, we recommend 355 +/- 8 kJ mol(-1) for the C-H BDE of 1,3-cyclopentadiene and 271 +/- 8 kJ mol(-1) for the enthalpy of formation of cyclopentadienyl radical.