Nucleophilic constant hybridization

Esters are formed in nucleophilic substitution reactions in which the nucleophile is a carboxylate anion. The anions of carboxylic acids are relatively weak nucleophiles towards sp3-hybridized carbon. Swain s nucleophilic constant, n, for acetate ion is 2.7183, slightly smaller than that for chloride. Thus acetate is selectively alkylated by alkyl halides in aqueous solution, e.g. 

Fig. 2.5(B) Expected NMR patterns for each intermediate. The chemical shift and the. /cN coupling of the carbonyl carbon signal of Pi residue must be very sensitive to the state of the complex. In the Michaelis I intermediate, the Pi carbonyl carbon should have the resonance in the carbonyl region and its coupling from l5N of Pi residue should be observed at about 15 Hz, since the scissile bond in this intermediate is normal peptide conformation. In the tetrahedral I intermediate, it should shift strongly upfield and the coupling constant should be decreased to 2-3 Hz, since the hybridization of the Pi carbonyl carbon changes from sp2 to sp3 by the nucleophilic addition of the y-O of active Ser of the proteinase. In the other three intermediates, Jcn should be diminished, since the scissile bond would not be bonded.

Macroscopic solvent effects can be described by the dielectric constant of a medium, whereas the effects of polarization, induced dipoles, and specific solvation are examples of microscopic solvent effects. Carbenium ions are very strong electrophiles that interact reversibly with several components of the reaction mixture in addition to undergoing initiation, propagation, transfer, and termination. These interactions may be relatively weak as in dispersive interactions, which last less than it takes for a bond vibration (<10 14 sec), and are thus considered to involve "sticky collisions. Stronger interactions lead to long-lived intermediates and/or complex formation, often with a change of hybridization. For example, onium ions are formed with -donors. Even stable trityl ions react very rapidly with amines to form ammonium ions [41], and with water, alcohol, ethers, and esters to form oxonium ions. Onium ion formation is reversible, with the equilibrium constant depending on the nucleophile, cation, solvent, and temperature (cf., Section IV.C.3). 

Me2pyo[14]trieneN4 (CR) ligand (Fig. 6a) catalyzes the hydrolysis of the triester diphenyl 4-nitrophenyl phosphate in aqueous acetonitrile solution.221 This reaction is first-order in zinc complex and phosphate ester. On the basis of pH-rate studies, which revealed a kinetic pifa value of 8.7,40 the active zinc complex is proposed to be [(CR)Zn-OH]+. A hybrid mechanism in which the zinc center of [(CR)Zn-OH]+ serves to provide the hydroxide nucleophile, and also electrophilically activates the phosphoryl P O bond, is favored for this system. This type of bifunctional mechanism was proposed based on the fact that the second-order rate constant for the [(CR)Zn-OH]+-catalyzed reaction (2.8 x 10 1 M-1 s 1) is an order of magnitude larger than that of free hydroxide ion-catalyzed hydrolysis (2.8 x 10 2M 1 s 1). As OH- is a better nucleophile than the zinc-coordinated hydroxide, Lewis acid activation of the substrate is also operative in this system. 

Kinetic studies of the reaction of a mononuclear N2S(thiolate)-ligated zinc hydroxide complex (PATH)Zn-OH with tris(4-nitrophenyl) phosphate in 33% ethanol-water and 7=0.10 (NaN03) also point to a hybrid-type mechanism (Fig. 43).228 Overall, this reaction is second order and a pH-rate profile indicates that the zinc hydroxide species (PATH)Zn-OH is involved in the reaction. The maximum rate constant for this reaction (16.1(7) M-1 s-1) is higher than that reported for free hydroxide ion (10.7 +0.2 M 1 s-1).225 This implies that a simple mechanism involving nucleophilic attack is not operative, as free OH- is a better nucleophile. Studies of the temperature dependence of the second-order rate constants for this reaction yielded activation parameters of A77 = 36.9(1) kJ mol-1 and AS = —106.7(4) JmolK-1. The negative entropy is consistent with considerable order in the transition state and a hybrid-type mechanism (Fig. 43, bottom). 

Nucleophilicity is a measure of how readily a compound (a nucleophile) is able to attack an electron-deficient atom. Nucleophilicity is measured by a rate constant (k). In the case of an Sn2 reaction, nucleophilicity is a measure of how readily the nucleophile attacks an sp hybridized carbon bonded to a leaving group. 

The Ce(IV) ion accelerates this process 10 fold. The proposed mechanism of DNA hydrolysis by the bimetallic cluster [Ce 2(OH)4] is schematically depicted on fig. 10. First, the phosphate residue is coordinated to the two Ce(IV) ions in [Ce 2(OH)4] + the apparent association constant between Ce(IV) and TpT was determined to be 10 M at pH 2.0 and 50 °C. As clearly evidenced by both spectroscopic and theoretical studies (cf. sects. 4.2 and 4.3), the electrons of the scissile phosphodiester linkage are strongly withdrawn by the Ce(IV) ions. Furthermore, the orbitals of this phosphate are mixed with the orbitals of the Ce(IV), and form new hybrid-orbital(s). These two factors greatly activate the phosphodiester linkage and make it highly susceptible to the attack by various nucleophiles. 

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