Solution acidity, computational chemistry

In textbooks of computational chemistry you will invariably find examples calculating the pH = - lg [H+]/(mol/l)> in weak acid - strong base or strong acid - weak base solutions. Indeed, these examples are important in the study of acids, bases and of complex formation, as well as for calculating titration curves. Following (ref. 24) we consider here the aquous solution that contains a weak tribasic acid H A and its sodium salts NaH, Na HA and Na A in known initial concentrations. The dissociation reactions and equilibrium relations are given as follows. 

R. Cammi, B. Mennucci, Structure and properties of molecular solutes in electronic excited states A polarizable continuum model approach based on the time-dependent density functional theory, in Radiation Induced Molecular Phenomena in Nucleic Acids A Comprehensive Theoretical and Experimental Analysis, ed. by M.K. Shukla, J. Leszczynski. Series Challenges and Advances in Computational Chemistry and Physics, vol 5 (Springer, Netherlands 2008)... 

MacKerell, A. D., Jr., Banavali, N. (2000). Allatom empirical force field for nucleic acids II. Application to molecular dynamics simulations of DNA and RNA in solution. Journal of Computational Chemistry, 21,105. 

The key challenge for computational chemistry with respect to the transmeta-lation step of the Suzuki-Miyaura cross-coupling was to understand the role of the external base. It is certainly well known from experiment that the presence of a base in solution is required for the reaction to take place. Several proposals have been put forward for the role of this base from experimental studies. Most of this information was summarized by Miyaura in a very clarilying paper [43], Two main pathways are proposed (Fig. 11.5) either the base binds the boronic acid to from the organoboronate species (path A), or the base substitutes the halide ligand in the coordination sphere of the catalyst (path B). These two proposed pathways were theoretically evaluated by us on a model system, using trans-PdBr(CH2 = CH)(PH3)2, CH2 = CH-B(OH)2 and OH species as reactants [44]. 

The generation of carbocations in strongly acidic media, and the characterization of their structure by NMR in the 1950s was a breathtaking accomplishment that led to the award of the Nobel Prize in Chemistry to George Olah. Over the past 50 years NMR spectroscopy has evolved as the most important experimental method for the direct study of structure and dynamics of carbocations in solution and in the solid state. Hans-Ullrich Siehl provides an excellent review of computational studies to model experimental NMR spectra for carbocations. This chapter provides an example of how the fruitful interplay between theory and experiment has led to a better understanding of an important class of reactive intermediates. 

Biochemistry and chemistry takes place mostly in solution or in the presence of large quantities of solvent, as in enzymes. As the necessary super-computing becomes available, molecular dynamics must surely be the method of choice for modeling structure and for interpreting biological interactions. Several attempts have been made to test the capability of molecular dynamics to predict the known water structure in crystalline hydrates. In one of these, three amino acid hydrates were used serine monohydrate, arginine dihydrate and homoproline monohydrate. The first two analyses were by neutron diffraction, and in the latter X-ray analysis was chosen because there were four molecules and four waters in the asymmetric unit. The results were partially successful, but the final comments of the authors were "this may imply that methods used currently to extract potential function parameters are insufficient to allow us to handle the molecular-level subtleties that are found in aqueous solutions" (39). 

As would be anticipated for a carboxylic acid, mandelic acid is known to exhibit a pH strong dependence in its aqueous solubility. This pH dependence was calculated using the solubility module of the ACD PhysChem computational program (version 6.0, Advanced Chemistry Development, Toronto, Canada), and these results are plotted in Figure 1. The results indicate that mandelic acid will be freely soluble in basic solution, which would be interpreted to imply that the sodium salt would be freely soluble as well. 

Most of the studies on the RE(III) complexes with neutral and basic amino acids have shown that complexation takes place when pH > 6, and that RE(OH)3 precipitation forms if the pH > 8, and experiments done at pH < 7 or 7.5 are considered to be free of significant hydrolysis. However, a few studies did show that protonated complex species form at pH < 2, and the hydrolysis of RE(III) starts at pH < 6 [126,135,136]. The large discrepancies among the data could be a result of different experimental conditions [concentrations of the RE(III) and the ligands, the RE L ratios] and various computing models used, as all of the experiments and the calculations are based on Bjerrum s method [142]. More detailed and systematic studies are thus definitely needed for the solution chemistry of RE(III)-amino acid complexes. 

Bonzom et al., 1997 Corey et al., 1983 Corey et al., 1979 Leach and Front, 1990 Rabinovich and Ripatti, 1991 Rich, 1993 Wilson et al., 1988). These computational studies of AA have primarily found looped or back-folded conformations to be low-energy conformers of AA. Rich conducted a quenched MD smdy of AA in vacuo (Rich, 1993). The two lowest enthalpy conformers found for AA were J-shaped conformers in which the carboxylic acid group is in close proximity to the C14—C15 Jt bond. This same J-shape was reported by Corey and co-workers (1983) as one type of low-energy minimum identified in their conformational analysis of AA. Corey suggested that such a J-shaped conformation in solution would be energetically favorable and would be consistent with the chemistry of peroxyarachidoiuc acid for which an internal epoxidation leads to 14, 15-epoxyarachidonic acid (Corey et al., 1979). 

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