Proton site differentiated

The protonation site of 2-pyrazolines has been determined as N(l) using 13C NMR spectroscopy. This behaviour is not followed for l-phenyl-3-aminopyrazolines which are protonated on N(2) <1995J(P2)1875>. 13C NMR spectroscopy easily differentiates the 1,1- and 1,2-disubstituted pyrazolinium cations 152 and 153... 

A Somogyi, VH Wysocki, I Mayer. The effect of protonation site on bond stmgths in simple peptides Application of ab initio and modified neglect of differential over-... 

Many definitions and descriptions of HAT, prior to the emergence of PCET as a field of study, did not adequately take into account the complexity embodied by Fig. 17.1. HAT is traditionally defined as the transfer of an electron and a proton from one location to another along a spatially coincidental pathway. In this case, the electron and proton are donated from one atom and they are accepted by another atom. These transfers are well described mechanistically as the diagonal pathway of Fig. 17.1 and they have been treated formally by a number of investigators [3, 4]. However, many reactions treated within a formalism of HAT are more complex as ET and PT are site-differentiated either along uni- or bidirectional pathways. As will be discussed in this chapter, traditional descriptions of HAT do not address how the electron and proton transfer events are coordinated mechanistically in these more complicated reactions and more general treatments of PCET are warranted. 

PCET can occur when the electron and proton are site-differentiated on both the donor and acceptor sides of the reaction. The PT coordinate must still be constrained to a hydrogen bond length scale, however, it is feasible for the ET coordinate to span an extended distance [79-81]. Nevertheless, coupling between the electron and proton may be strong since the redox potentials depend on the protonation state and the pfQ,s depend on the redox state. Consequently, the square scheme of Eig. 17.1 must be used to evaluate the attendant thermodynamics. 

Type A PCET reactions describe amino acid radical generation steps in many enzymes, since the electron and proton transfer from the same site as a hydrogen atom [188]. Similarly, substrate activation at C-H bonds typically occurs via a Type A configuration at oxidized cofactors such as those in lipoxygenase [47, 48] galactose oxidase [189-191] and ribonucleotide reductase (Y oxidation at the di-iron cofactor, vide infra) [192]. Here, the HATs are more akin to the transition metal mediated reactions of Section 17.3.1 since the final site of the electron and proton are on site differentiated at Ae (redox cofactor) and Ap (a ligand). 

It is often difficult to determine the nature of the adsorbed species, or even to distinguish between the different kinds of adsorbed species from the calorimetric data. In many cases this technique fails to distinguish between cations md protonic sites due to the insufficient selectivity of the adsorption. For example, the differential heats of NH3 adsorption on strong Lewis centres and strong Brdnsted sites are relatively close to each other. This can make it difficult in some cases to discriminate Lewis and Bronsted sites solely by adsorption microcalorimetry of basic probe molecules if no complementary techniques are used. Because no exact information can be obtained regarding the nature of the acid centres from the calorimetric measurements, suitable IR, MAS NMR, and/or XPS [36] investigations are necessary to identify these sites. However,... 

N centers. Peresypkin et al. differentiated protonated and non-protonated sites using low power decoupling to eliminate signals effectively from the strongly coupled NH groups." ... 

Evaluation of the only appropriate Fukui function is required for investigating an intramolecular reaction, as local softness is merely scaling of Fukui function (as shown in Equation 12.7), and does not alter the intramolecular reactivity trend. For this type, one needs to evaluate the proper Fukui functions (/+ or / ) for the different potential sites of the substrate. For example, the Fukui function values for the C and O atoms of H2CO, shown above, predicts that O atom should be the preferred site for an electrophilic attack, whereas C atom will be open to a nucleophilic attack. Atomic Fukui function for electrophilic attack (fc ) for the ring carbon atoms has been used to study the directing ability of substituents in electrophilic substitution reaction of monosubstituted benzene [23]. In some cases, it was shown that relative electrophilicity (f+/f ) or nucleophilicity (/ /f+) indices provide better intramolecular reactivity trend [23]. For example, basicity of substituted anilines could be explained successfully using relative nucleophilicity index ( / /f 1) [23]. Note however that these parameters are not able to differentiate the preferred site of protonation in benzene derivatives, determined from the absolute proton affinities [24],... 

Fig. 31 a, b. Proton ENDOR spectrum of two overlapping sites of Cu(sal)2. a) Arrow indicates the choice of the B0 field position in the EPR spectrum, b) Differentiation of ENDOR signals of overlapping sites by means of the phases of their signals. (Adapted from Ref. 62)... 

The pretreatment temperature is an important factor that influences the acidic/ basic properties of solids. For Brpnsted sites, the differential heat is the difference between the enthalpy of dissociation of the acidic hydroxyl and the enthalpy of protonation of the probe molecule. For Lewis sites, the differential heat of adsorption represents the energy associated with the transfer of electron density toward an electron-deficient, coordinatively unsaturated site, and probably an energy term related to the relaxation of the strained surface [147,182]. Increasing the pretreatment temperature modifies the surface acidity of the solids. The influence of the pretreatment temperature, between 300 and 800°C, on the surface acidity of a transition alumina has been studied by ammonia adsorption microcalorimetry [62]. The number and strength of the strong sites, which should be mainly Lewis sites, have been found to increase when the temperature increases. This behavior can be explained by the fact that the Lewis sites are not completely free and that their electron pair attracting capacity can be partially modified by different OH group environments. The different pretreatment temperatures used affected the whole spectrum of adsorption heats... 

However, new types of radiation continue to be explored with the aim of improving the physical selectivity, the radiobiological differential effect, or both. In this context, the role of fast neutrons with their biological selectivity in selected cancer sites and of protons with their superb physical selectivity will be reviewed. 

CA has been the snbject of numerous theoretical studies, most of which have centered on differentiating between the Lipscomb and Lindskog mechanisms or on the proton-transfer step. Early studies concentrated on substrate binding and simple models for the active site jqqj, mechanistic studies on model active sites were being published229.254- 268 suggested quite early that active-site water molecules may... 

As was noted in Section 1.3.2.A, one-electron oxidation causes deprotonation of cation radicals. Cation radicals bearing protons that are (3 to a site of charge/spin density are superacids. Because of this feature, attention must be given to the distinction between cation radical and H-acid catalysis of cycloaddition. Bauld s group has elaborated a set of criteria that allow one to differentiate these mechanisms one from another (Reinolds et al. 1987). 

IR spectra of dialkynyl-A3-iodane 75 differentiate the two alkynyl groups, occupying apical (2187 cm-1) and equatorial (2152 cm-1) sites, while the and 13C NMR spectra display only single resonances for each of the different protons and carbons, probably due to degenerate isomerization by rapid pseudorotation on the iodine [114]. 

When mixed with equimolar amounts of the dirhodium complex 22, the enantiomers of mesoionic 1,2,3,4-oxatriazoles 19-21 can be differentiated by proton NMR <2003MRC315>. The negatively charged exocyclic nitrogen atom provides the binding site to the rhodium complex <2003MRC921>. 

On a molar basis, most organic compounds contain similar amounts of hydrogen and carbon, and processes involving transfer of hydrogen between covalently bound sites rank in importance in organic chemistry second only to those involving the carbon-carbon bond itself. Most commonly, hydrogen is transferred as a proton between atoms with available electron pairs (l), i.e. Bronsted acid/base reactions. The alternative closed shell process, hydride transfer or shift, involves motion of a proton with a pair of electrons between electron deficient sites (2). These processes have four and two electrons respectively to distribute over the three atomic centres in their transition structures. It is the latter process, particularly when the heavy atoms are both first row elements, which is the subject of this review. The terms transfer and shift are used here only to differentiate intermolecu-lar and intramolecular reactions. 

The alanine racemization catalyzed by alanine racemase is considered to be initiated by the transaldimination (Fig. 8.5).26) In this step, PLP bound to the active-site lysine residue forms the external Schiff base with a substrate alanine (Fig. 8.5, 1). The following a-proton abstraction produces the resonance-stabilized carbanion intermediates (Fig. 8.5, 2). If the reprotonation occurs on the opposite face of the substrate-PLP complex on which the proton-abstraction proceeds, the antipodal aldimine is formed (Fig. 8.5,3). The subsequent hydrolysis of the aldimine complex gives the isomerized alanine and PLP-form racemase. The random return of hydrogen to the carbanion intermediate is the distinguishing feature that differentiates racemization from reactions catalyzed by other pyridoxal enzymes such as transaminases. Transaminases catalyze the transfer of amino group between amino acid and keto acid, and the reaction is initiated by the transaldimination, followed by the a-proton abstraction from the substrate-PLP aldimine to form a resonance-stabilized carbanion. This step is common to racemases and transaminases. However, in the transamination the abstracted proton is then tranferred to C4 carbon of PLP in a highly stereospecific manner The re-protonation occurs on the same face of the PLP-substrate aldimine on which the a-proton is abstracted. With only a few exceptions,27,28) each step of pyridoxal enzymes-catalyzed reaction proceeds on only one side of the planar PLP-substrate complex. However, in the amino acid racemase... 

The two sites also differ in their pH stability towards iron release. Experiments on serum transferrin showed that one site loses iron at a pH near 6.0, and the other at a pH nearer 5.0 (203, 204), giving a distinctly biphasic pH-induced release profile (Fig. 28). The acid-stable A site was later shown to be the C-terminal site (202). It is this differential response to pH, together with kinetic effects (below), that enables N-terminal and C-terminal monoferric transferrins to be prepared (200). Although the N-terminal site is more labile, both kinetically and to acid, the reasons are not necessarily the same the acid stability may depend on the protonation of specific residues (Section V.B) and is likely to differ somewhat from one transferrin to another in response to sequence changes. The biphasic acid-induced release of iron seen for transferrin is not shared by lactoferrin. Although biphasic release from lactoferrin, in the presence at EDTA, has been reported (205), under most conditions both sites release iron essentially together at a pH(2.5-4.0) several units lower than that for transferrin (Fig. 28). 

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