Polarization, group

What does functional-group polarity mean with respect to chemical reactivity Because unlike charges attract, the fundamental characteristic of all polar organic reactions is that electron-rich sites react with electron-poor sites. Bonds are made when an electron-rich atom shares a pair of electrons with an electron-poor atom, and bonds are broken when one atom leaves with both electrons from the former bond. 

FIGURE 3.5 Orientation of soap (surface-active substance) at the surface of water (alkyl group —, polar group 0). 

Cationic detergent + hair ----alkyl group. .. polar group(+)hair(-)... 

Physical and Chemical Integrity of Proteins. The primary sequence of proteins and peptides is comprised of L-amino acids linked together by covalent amide bonds. Substituent group polarity and/or charge is a critical determinant of secondary and tertiary structure and stability. Secondary structures (a-helices and P-sheets) arise from hydrophobic, ionic, and Van der Waals interactions that fold the primary amino acid chain upon itself. Most therapeutic proteins exhibit tertiary structure vital to functionality and are held together by covalent and noncovalent bonding of secondary structures (Figure 5.2). 

Solvent effects Different solvents have different effects on the nucleophilicity of a species. Solvents with acidic protons are called protic solvents, usually O—H or N—H groups. Polar protic solvents, e.g. dimethyl sulph-oxide (DMSO), dimethyl formamide (DMF), acetonitrile (CH3CN) and acetone (CH3COCH3) are often used in 8 2 reactions, since the polar reactants (nucleophile and alkyl halide) generally dissolve well in them. 

Bonded group Polarity Retention mechanisms Comments... 

They are thus independent of group polarity, and are genuine measures of steric effects. 

However, it was immediately recognized by peptide chemists that, even in the cases where a direct (backbone)peptide -protein(backbone) interaction is not operative, the backbone conformation may dramatically influence the biological response. It is evident that the introduction of new, promising peptidomimetics is based primarily on the combined knowledge of the complementary conformational, topochemical, and electronic properties of the native peptide and of its address (in other words, of the receptor or the active site of the enzyme with which it interacts). Then, the design of peptidomimetics as potential bioactive compounds must take into particular account two structural factors (i) a favorable fit (tertiary structure) with respect to the corresponding complementary spatial situation at the active site (ii) the placement of structural elements (e.g., functional groups, polar and... 

Fig. 90. (A) Glycine-tyrosine bound to carboxypeptidase (443). Indirect attack of Glu-270 promotes the attack of a water molecule on the amido carbonyl group polarized by interaction with zinc. (B) Direct attack of Glu-270 on the amido carbonyl with formation of an anhydride.

Initiated by Stork and co-workers,47 the scope and stereochemistry of enamine alkylations have been well explored. In general, good stereoselectivities can be obtained using bulky directing groups, polar aprotic solvents, and low temperatures. 

Within any functional group, polarity decreases rapidly as the length of the nonpolar carbon chain increases. The polarity of mixed solvents is intermediate between the respective polarities of individual solvents of which they are composed. 

It is useful to divide the solvents into three groups polar solvents that are not water, nonpolar solvents, and cryosolvents. 

In mixed trifluoroacetic anhydrides, the strong electron-withdrawing tri-fluoroacetyl group polarizes the bonds to the anhydride oxygen in such a way that it tends to split to acylium cation and trifluoroacetate anion [/0/. Generally, the products of the reaction of hydroxy compounds with acyl trifluoroacetates are esters of carboxylic acids and trifluoroacetic acid, because the acyl carbonyl is better fit for a nucleophilic attack than the carbonyl next to the trifluoromethyl group [707]. 

The strong inductive effect of the three trifluoromethyl groups polarizes the bond between the carbon and hydrogen and makes the hydrogen very acidic (pKa = 7). In basic media, the compound is deprotonated, and the tris(trifluoromethyl)carbanion adds to the double bond of acrylonitrile in the sense of the Michael addition. It joins the P-position of acrylonitrile because of its lower electron density. The product is 4,4-bis(trifluoro-methyl)-5,5,5-trifluorovaleronitrile T [107],... 

However, if two trifluoromethyl groups are attached to the beta carbon, the cumulative effect of the two trifluoromethyl groups polarizes the double bond so that lower electron density is in alpha position, and the nucleophile becomes attached to the alpha carbon. The reaction product is L, ethyl 2-(P-hydroxyethylamino)-3-trifluoromethyl-4,4,4-tri-fluorobutanoate [117]. 

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