Configuration in solution

FIGURE 6.10. Comparing the energetics of the EVB configurations in solution and in the active site of lysozyme. The calculations were done by using the PDLD and related models (Refs. 6 and 7) and they represent a study of a stepwise mechanism. The energetics of a more concerted pathway (e.g., that of Fig. 6.9) is almost identical to that of the stepwise mechanism and correlated in a similar way with the electrostatic effect of the protein. 

Addition of CO to Ir(S03F)3 dissolved in HS03F gives crystals of / /e/--[Ir(CO)3(S03F)3].230 IR spectroscopy and X-ray structural determination confirm the mer configuration. In solution (HS03F) there is evidence (IR and NMR) of a mixture of mer- and /uc-isomers. 

Dombrow and Beckmann163 have carried out ultracentrifugal and viscometric studies of several amylose acetates in methyl acetate solution. Their data, shown in Table VI, were interpreted as supporting the idea of a helical configuration in solution. 

The absolute values of the absorption energy for different configurations in solution can vary substantially (d = 0.3-0.4 eV). Comparison of ROKS and TDDFT values shows that both techniques predict very similar relative variations although their absolute values are shifted by a constant amount. 

The total potential energy of the localized, VB-like configuration in solution is thus computed by solving the seeular equation by diagonalizing the Hamiltonian matrix, if, to yield... 

In pioneering NMR work (see Section 5.21.2.2) Simmons and Park showed that uncom-plexed diazabicycloalkanes (N[(CH2)fc,i>m]N), the parents of cryptands, can exist in three different configurations in solution the exo-exo in which both nitrogen lone pairs point away from the cavity, the endo-endo in which both lone pairs point into the cavity and the intermediate exo-endo with one lone pair inside and the other outside (Figure 6). 

However, whether or not a molecular interaction rests on one dominant configuration in solution cannot be deduced easily. The problem touches on the fundamental issue of structure-energy correlation, and is heavily loaded with justified and/or completely arbitrary presumptions that in many cases reflect a traditional bias rather than a well-balanced appreciation of scientific arguments. 

Interestingly, the two methods published for quantification of sunitinib used either HPLC [114] or UPLC [113] but the analytical time periods were of similar duration (run time of 3 min and 4 min, respectively). Of note, we observed during the course of our own method development [122] the presence of two peaks with the same molecular mass/signal transition for sunitinib, which, to the best of our knowledge, has not been reported elsewhere [113, 114, 123], The phenomenon was known, however, and is due to a Z-E isomerization reaction of sunitinib [124], Previous studies by the sunitinib manufacturer have shown that E isomer can be generated from the Z isomer in a reversible manner in solution [124], The rate of interconversion between the Z-E configurations in solution is dependent on a number of factors, most notably exposure to light. In our studies [122], we found that both isomers could be detected in the pharmaceutical preparation (tablet) at ratios of about 1 2, as well as in patients plasma samples (variable ratios). 

The dynamic stereochemistry of spiroarsoranes containing five- and six-membered ring systems has also been studied by Dale and Froyen (44). The variable-temperature NMR results have been interpreted in terms of pseudorotation processes. It has been concluded that the observed spectra do not allow deduction as to whether trigonal-bipyra-midal, rectangular-pyramidal, or any other intermediate structure is the most stable configuration in solution (44, 45). 

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