General acid-base catalysis of complex reactions in water

Jencks, William P.

doi:10.1021/cr60280a004

Cited by 498 publications

(310 citation statements)

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“…The best way around this problem is by describing the full free-energy surface by means of a More O'Ferrall-Jencks (MFJ) diagram (Jencks, 1972 ;More O'Ferrall, 1970). By definition, this involves the visualization of the free-energy surface of a reacting system as a function of two given coordinates.…”

Section: Free-energy Surfaces Provide the Most Unique Mechanistic Defmentioning

confidence: 99%

Why nature really chose phosphate

Kamerlin

Sharma

Prasad

et al. 2013

Quart. Rev. Biophys.

334

448

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Phosphoryl transfer plays key roles in signaling, energy transduction, protein synthesis, and maintaining the integrity of the genetic material. On the surface, it would appear to be a simple nucleophile displacement reaction. However, this simplicity is deceptive, as, even in aqueous solution, the low-lying d-orbitals on the phosphorus atom allow for eight distinct mechanistic possibilities, before even introducing the complexities of the enzyme catalyzed reactions. To further complicate matters, while powerful, traditional experimental techniques such as the use of linear free-energy relationships (LFER) or measuring isotope effects cannot make unique distinctions between different potential mechanisms. A quarter of a century has passed since Westheimer wrote his seminal review, ‘Why Nature Chose Phosphate’ (Science 235 (1987), 1173), and a lot has changed in the field since then. The present review revisits this biologically crucial issue, exploring both relevant enzymatic systems as well as the corresponding chemistry in aqueous solution, and demonstrating that the only way key questions in this field are likely to be resolved is through careful theoretical studies (which of course should be able to reproduce all relevant experimental data). Finally, we demonstrate that the reason that naturereallychose phosphate is due to interplay between two counteracting effects: on the one hand, phosphates are negatively charged and the resulting charge-charge repulsion with the attacking nucleophile contributes to the very high barrier for hydrolysis, making phosphate esters among the most inert compounds known. However, biology is not only about reducing the barrier to unfavorable chemical reactions. That is, the same charge-charge repulsion that makes phosphate ester hydrolysis so unfavorable also makes it possible to regulate, by exploiting the electrostatics. This means that phosphate ester hydrolysis can not only be turned on, but also be turned off, by fine tuning the electrostatic environment and the present review demonstrates numerous examples where this is the case. Without this capacity for regulation, it would be impossible to have for instance a signaling or metabolic cascade, where the action of each participant is determined by the fine-tuned activity of the previous piece in the production line. This makes phosphate esters the ideal compounds to facilitate life as we know it.

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Section: Free-energy Surfaces Provide the Most Unique Mechanistic Defmentioning

confidence: 99%

Why nature really chose phosphate

Kamerlin

Sharma

Prasad

et al. 2013

Quart. Rev. Biophys.

334

448

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“…All of these mechanisms have been identified and characterized (Jencks & Carriuolo, 1959bJencks, 1972).…”

Section: "High Energy" Acyl and Phosphate Compoundsmentioning

confidence: 99%

Reaction mechanisms, catalysis, and movement

Jencks

1994

Protein Science

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“…It has been established that the majority of the reactions proceed by way of the E2 mechanism following the anti pathway (5,7). Experimental studies (8)(9)(10)(11)(12)(13)(14) have demonstrated that the structures of the respective E2 transition states vary significantly in accord with theoretical re dictions (15)(16)(17)(18)(19)(20).The reaction of the 2-arylethyl quaternary ammonium ions with base has been-shown to have considerable carbanionic character at the E2 transition state ( 1 , I 1,21), while the corresponding reaction of the 2-phenylethyl halides has been considered (1 1,16) to involve a more central E2 transition state where the extent of the carbon-hydrogen and carbon -leaving group bond rupture processes has progressed in a more synchronous fashion.In order to gain a direct measure of the relative amount of hybridization change at the a carbon at the E2 transition state (double-bond character), we have determined the secondary a-deuterium kinetic isotope effects for the reaction of the 2-phenylethyl halides with tert-butoxide in tert-butyl alcohol at 40°C, eq. [I].…”

mentioning

confidence: 62%

mentioning

confidence: 93%

Secondary α-deuterium kinetic isotope effects for the E2 reaction of the 2-phenylethyl halides with tert-butoxide ion in tert-butyl alcohol

Smith¹,

Rangappa²,

Westaway³

1985

Can. J. Chem.

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PETER JAMES SMITH, KANCHUGARAKOPPAL S. RANGAPPA, and KENNETH CHARLES WESTAWAY. Can. J. Chem. 63, 100 (1985).Secondary a-deuterium kinetic isotope effects have been determined for the elimination reactions of 2-phenylethyl halides with tert-butoxide in tert-butyl alcohol at 40°C in the presence and absence of the crown ether 18C6. The second-order rate constant k, and the normal (kt'/kD), effect remained constant when the tert-butoxide concentration was varied for reaction of the iodo and bromo compounds. However, both the magnitude of k, and the secondary a-deuterium isotope effect were significantly dependent on [t-BuO-] when chlorine and fluorine are the leaving groups. It is noteworthy that (kH/k"),, is inverse for the reaction of both the chloro and fluoro compounds at "low" base concentrations and normal at "high" base concentrations. These results are discussed in terms of both syn-and anti-elimination pathways promoted by various associated and dissociated base species. It is suggested that the (kH/k"),, effect may be useful as a criterion for determining the stereochemistry of E2 elimination reactions.PETER JAMES SMITH, KANCHUGARAKOPPAL S. RANGAPPA et KENNETH CHARLES WESTAWAY. Can. J . Chem. 63, 100 (1985). Operant 3 40°C et en prtsence ou en I'absence de I'tther couronne 18C6, on a dttermink les effets isotopiques cinttiques secondaires des deuterium en a sur les reactions d'klimination des halogtnures de phenyl-2 Cthyles par la tert-butylate dans I'alcool tert-butylique. Dans les cas des compos6s iodCs ou bromCs, la constante de vitesse du deuxikme ordre (kZ) ainsi que I'effet normal (kH/k"),, demeurent constants lorsqu'on fait varier la concentration du tert-butylate. Toutefois, lorsque les groupes nucltofuges sont soit Ie fluor ou le chlore, ['amplitude de k2 ainsi que I'effet isotopique secondaire des deuterium en a varient d'une f a~o n importante avec la concentration de I'ion tert-butylate. I1 est notable que, pour les rkactions des composts fluorCs ou chlorCs 3 de "basses" concentrations de base, la valeur (kl'/k"),, est inverse; toutefois, h des concentrations "ClevCes" de base, cette valeur est normale. On discute de ces resultats en fonction de voies d'eliminations syn et anti qui sont PavorisCes par diverses cspkces basiques associCcs et dissocites. On suggkre que I'effet (kk'/k"),, pourrait etre un critkrc utile pour dCterminer la sttrtochimie des rCactions dlCliminations E2.[Traduit par le journal]The elimination reaction of the 2-arylethyl derivatives with different leaving groups Y, ArCH,CH,Y, has been extensively studied (1 -6) under a variety of solvent/base conditions. It has been established that the majority of the reactions proceed by way of the E2 mechanism following the anti pathway (5,7). Experimental studies (8)(9)(10)(11)(12)(13)(14) have demonstrated that the structures of the respective E2 transition states vary significantly in accord with theoretical re dictions (15)(16)(17)(18)(19)(20).The reaction of the 2-arylethyl quaternary ammonium ions with base has been-shown to h...

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General acid-base catalysis of complex reactions in water

Cited by 498 publications

References 6 publications

Why nature really chose phosphate

Why nature really chose phosphate

Reaction mechanisms, catalysis, and movement

Secondary α-deuterium kinetic isotope effects for the E2 reaction of the 2-phenylethyl halides with tert-butoxide ion in tert-butyl alcohol

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