Solvent and pH Effects

The results on the values of the cis/trans equilibrium of simple amides in different solvents confirm observations made with Gly-Pro and acetyl-Gly-Pro-OMe [53,54], In all these cases the free energy difference for the isomers originates primarily from enthalpic differences. According to AH0 values obtained in different solvents, it was concluded that the enthalpic component that differentiates the cis and trans isomer is similar in protic and aprotic solvents. Thus, the entropic term was found to favor the cis isomer in both aqueous buffers and aprotic organic solvents. 

Interaction of peptides with Li+ ions in dry solvents, such as trifluorethanol (TFE) and tetrahydrofurane, can dramatically influence the free energy difference that discriminates the cis from the trans isomers for both prolyl bonds and secondary amide peptide bonds [56-59]. However, the Li+-induced increase of the cis isomer population in linear oligopeptides depends on the nature of the amino acids preceding proline (G. Fischer, unpublished results). 

Specific acid catalysis is also restricted to biologically noncompatible conditions because amides are protonated in oxygen rather than nitrogen with pKa values in the range of 0 [63,64]. The rarity of intermolecular acid/base effects on CTI was affirmed by the kinetic deuterium solvent isotope effects (KSIE) of about 1.0, indicating that the mechanism of spontaneous isomerization does not involve a proton-in-flight [29,42,65]. 

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The contribution neighbor anisotropy effect. This term accounts for the fields arising from electronic circulations around the atoms surrounding the observed nucleus. It depends on the nature of the neighbor atoms and on molecular geometry. Sometimes, a medium term must be added in eq. (3.2), correcting for solvent and pH effects. 

As a general rule, C-2 of oxygen- and nitrogen-containing rings is further to the left than C-3. Large solvent and pH effects have been recorded. Table 4.13 gives values for neat samples of several five- and six-membered heterocyclic compounds. 

Amorati, R., Pedulli, G.F., Cahrini, L., Zambonin, L., Laudi, L. Solvent and pH effects on the antioxidant activity of caffeic and other phenolic acids. J. Agric. Food. Chem. 54, 2932 (2006)... 

Solvents and pH may have a marked effect on stereochemistry as was illustrated in Chapter 1, and the generality given there is useful, A further example of the stereochemical influence that may be exerted by proper choice of catalyst and solvent is shown in the hydrogenation of a complex enamine, By proper choice of conditions high yields of either the cis or trans product could be obtained. Selected results are shown below (52) (data used with permission). 

Maiti PK, Cagin T, Lin S-T, Goddard III WA. Effect of solvent and pH on the structure of PAMAM dendrimers. Macromolecules 2005 38 979-991. 

In the case of fluorescence spectra, it is the emission of the radiation from the excited state that is measured, rather than its absorption. This also provides valuable information. As an example, tetraethylorthosilicate (TEOS)-based gels were doped with two optically active organic indicators, thionin and nile blue A. Before trapping in a solgel host, thionin and nile blue A were both evaluated for solvent and protonation effects on their spectral properties. Only extreme pH values provided by HCl, NaOH, and NH4OH produced new absorption and/or fluorescence bands. The absorption and fluorescence spectra revealed a decrease in a pH 11 solution of NH4OH compared to neutral conditions (Krihak et al., 1997). 

The key operational parameter in free-solution capillary electrophoresis is the pH of the running buffer, as the electroosmotic flow and ionization of the analyte can be regulated by this variable. The role of buffers in capillary electrophoresis has been discussed in detail, with emphasis on buffer concentration, buffer type, and pH effects [10]. The effect of organic solvents on separation and migration behavior has been studied for dipeptides [11] and somatostatin analog peptides [12]. The order of migration as well as the selectivity may be manipulated by organic modifiers in... 

NMR spectral parameters, that is, chemical shift (8) and coupling constant (J), may be considerably affected by the sample condition, that is, solvent, pH, sample temperature, concentration, and choice of internal and/or external chemical shift references. Solvent and pH (in water/D20 samples) have the greatest effect. The sample condition should therefore be the same as or comparable to that used for the authentic reference chemical (or library spectrum) and the blank sample. 

Saracino GAA, Tedeschi A, D Errico G, Improta R, Franco L, Ruzzi M, Corvaia C, Barone V (2002) Solvent polarity and pH effects on the magnetic properties of ionizable nitroxide radicals A combined computational and experimental study of 2,2,5,5-tetramethyl-3-carboxypyrrolidine and 2,2,6,6-tetramethyl-4-carboxypiperidine nitroxides. J Phys Chem A 106 10700-10706... 

Piperidines and related systems have a number of (potentially) readily accessible conformations. In nipecotic acid 141 a hydrogen bond stabilizes the axial conformation 142. Both conformations have been detected by H NMR spectroscopy at low temperature and their spectra fully documented together with the effect of solvent and pH <2000J(P2)2382>. 

In summary, one may thus conclude from evidence provided by a variety of correlative methods that polypeptide chains assume a helical form in solution for clearly specified ranges of solvent polarity or pH. This result is in complete harmony with the structural proposal of Pauling et al. (1951) that polypeptide helices are stabilized by intramolecular hydrogen bonds, since competition for hydrogen bonds by polar solvents and electrostatic effects that influence this competition in water lead to disruption of these rodlike structures. Polypeptide helices of varying composition and different solvent requirements for helical stability appear, moreover, to have in common a specifically a-helical conformation that persists from the solid state into solution. 

C- and N- nitroso compounds may exist as two Z and E (major) isomers due to the tautomeric effect which restricts the rotation about the C-N and N-N bonds. Thus CTI can occur via free rotation of the tautomeric form, doublet inversion etc. [29,14]. In this respect, C-nitroso compounds are the tautomeric form of the corresponding oximes (CH-N=0 —> C=N-OH). The energy barrier is usually between 12 and 27 kcal mol-1 [32], however, many factors may influence CTI, such as substituents, solvents, and pH [33]. For example, alkyl-substituted C- and N-nitroso compounds usually exist as a mixture of Z and E isomers [33], whereas acylnitroso [34] and nitrosocarbamate [35] species have an exclusive E relative stereochemistry due to oxygen-oxygen electronic repulsion. 

For UV analyses, the sample and the calibration standard must be dissolved in the same solvent to eliminate solvent effects on the UV absorbance. The sample and standard must also have similar pH. For many organic compounds, the UV absorbance maximum undergoes major shifts depending on the solvent and pH conditions. When the UV spectrum shifts to longer wavelengths it is termed a... 

The search for luminescent dyes suitable for use as solar energy collectors has lead to a detailed examination of the effects of solvent and pH on the spectral characteristics of Schiff s base... 

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