F. H. Westheimer

Phosphate esters and anhydrides dominate the living world but are seldom used as intermediates by organic chemists. Phosphoric acid is specially adapted for its role in nucleic acids because it can link two nucleotides and still ionize; the resulting negative charge serves both to stabilize the diesters against hydrolysis and to retain the molecules within a lipid membrane. A similar explanation for stability and retention also holds for phosphates that are intermediary metabolites and for phosphates that serve as energy sources. Phosphates with multiple negative charges can react by way of the monomeric metaphosphate ion PO3- as an intermediate. No other residue appears to fulfill the multiple roles of phosphate in biochemistry. Stable, negatively charged phosphates react under catalysis by enzymes; organic chemists, who can only rarely use enzymatic catalysis for their reactions, need more highly reactive intermediates than phosphates.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Magnitude of the Primary Kinetic Isotope Effect for Compounds of Hydrogen and Deuterium.F. H. WestheimerCite this: Chem. Rev. 1961, 61, 3, 265–273Publication Date (Print):June 1, 1961Publication History Published online1 May 2002Published inissue 1 June 1961https://pubs.acs.org/doi/10.1021/cr60211a004https://doi.org/10.1021/cr60211a004research-articleACS PublicationsRequest reuse permissionsArticle Views7733Altmetric-Citations680LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Abstract. The hydrolysis of a phosphate, phosphonate or phosphinate ester gen-eraUy takes place either through a trigonal bipyramidal hydroxyphosphorane as intermediate (with expansion of the coordination number of phosphorus from four to five) or (at least for phosphates) through a moaomeric metaphosphate as inter-mediate (with contraction of the coordination number of phosphorus from four to three). These processes parai.lel the principal mechanisms for the hydrolysis of carboxylic esters, which require either the formation of a tetrahedral interme-diate or that of an acylium cation.

Bjerrum's theory of the influence of substituents on dissociation constants has been extended and amplified. The molecules and ions entering into the ionization equilibria are treated as cavities of low dielectric constant, rather than as structureless regions of the same dielectric constant as the solvent. The theory gives better results than the simple Bjerrum formulation, especially for the short chain dicarboxylic acids, and in the fact that it permits a satisfactory treatment of the influence of dipolar substituents on dissociation constants.

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More