Transfer free energies, cyclohexane

Maccallum, J. L. Tieleman, D. P., Calculation of the water-cyclohexane transfer free energies of neutral amino acid side-chain analogs using the OPLS all-atom force held, J. Comput. Chem. 2003, 24, 1930-1935. 

FIGURE 6.2 Amino acid side chain analog insertion profiles with explicit (red) and implicit (purple, black) membrane models. The explicit lipid profiles were calculated with the OPLS force field [87], implicit profiles were calculated with both CHARMM [92] and OPLS force fields [93]. Experimental water-cyclohexane transfer free energies [85] are indicated as red dots. 

While the PM3-SM4 model does appear to slightly underestimate the polarity of the enol component, there is some cancellation of errors upon considering the differential transfer free energies between cyclohexane and water. As noted above, experiment indicates that the differential free energy of transfer of the dione and the enol is 3.1 kcal/mol the PM3-SM4 model predicts this value to be 2.8 kcal/mol, in excellent quantitative agreement. AM1-SM4 is less satisfactory in this regard, predicting only 1.9 kcal/mol. 

At temperatures well below UCST, solubilities of hydrocarbons in water or water in hydrocarbons drop to very low values. The solutions are very nearly ideal in the Henry s law sense, and the isotope effects on solubility can be directly interpreted as the isotope effect on the standard state partial molar free energy of transfer from the Raoult s law standard state to the Henry s law standard state. Good examples include the aqueous solutions of benzene, cyclohexane, toluene,... 

Free energies of transfer at 25°C and pH 7.0, adjusted for the effects of ionization, assuming that ionized forms move entirely into the aqueous phase. The difference between these two sets (i.e., the value for vapor— cyclohexane transfer) is presumably a measure of susceptibility to van der Waals attractions and seems to be simply related to surface area. A. Radzicka and R. Wolfenden, Biochemistry 27,1664-1670 (1988) R. Wolfenden, L. Andersson, P. M. Cullis, and C. C. B. Southgate, Biochemistry 20, 849-855 (1981) P. R. Gibbs, A. Radzicka, and R. Wolfenden, J. Am Chem. Soc. 118, 6105 (1996) 113, 4714-4715 (1991) and A. Radzicka, G. B. Young, and R. Wolfenden, Biochemistry 32,6807-6809 (1993). 

The [Ruv(N40)(0)]2+ complex is shown to oxidize a variety of organic substrates such as alcohols, alkenes, THF, and saturated hydrocarbons, which follows a second-order kinetics with rate = MRu(V)][substrate] (142). The oxidation reaction is accompanied by a concomitant reduction of [Ruv(N40)(0)]2+ to [RuIII(N40)(0H2)]2+. The mechanism of C—H bond oxidation by this Ru(V) complex has also been investigated. The C—H bond kinetic isotope effects for the oxidation of cyclohexane, tetrahydrofuran, propan-2-ol, and benzyl alcohol are 5.3 0.6, 6.0 0.7, 5.3 0.5, and 5.9 0.5, respectively. A mechanism involving a linear [Ru=0"H"-R] transition state has been suggested for the oxidation of C—H bonds. Since a linear free-energy relationship between log(rate constant) and the ionization potential of alcohols is observed, facilitation by charge transfer from the C—H bond to the Ru=0 moiety is suggested for the oxidation. 

Figure 4. Free-energy changes obtained from measured equilibrium constants in MTHF for the electron transfer reaction B SN BSN, where B = biphenyl, N = naphthalene, and S is a rigid, saturated hydrocarbon spacer group varying from 1,3-cyclohexane to the steroid 3,16-androstane. Also shown are calculated AG °s for charge separation and recombination, D + A - A, in moderately...

The first to propose a rather simple way to overcome these difficulties was Franck (49), who linearly correlated free energies of inert substituents in cyclohexane, AG, and tetrahydropyran [at C(2)], AG. He found that if such a substituent is transferred from cyclohexane to the anomeric C(2) carbon in tetrahydropyran, AG increases about 1.53 times (Eq. [3]) simply because of the increase in steric hindrance. Thus... 

J. Hermans A recent article (Hine and Mookerjee J. Org. Chem. 40, 292, 1975) correlates experimental data which show that the free energy of transfer of hydrocarbons from the vapor to an aqueous solution is near zero, i.e. a molecule such as cyclohexane is equipartioned between vacuum and water. This means that dispersion energies calculated for a model of, say, a protein, in vacuo give in first approximation an adequate description of what are normally called hydrophobic forces. The problem to be faced is to model adequately the interactions between polar groups and solvent and the effect of solvent as a dielectric on the interaction between charges on the modeled molecule. 

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