I thought it would be good to start the week by highlighting a particularly praiseworthy anion. That anion is phosphate, sometimes called orthophosphate, PO4 (3-).
So, you ask, what is so bloody interesting about phosphate? Isn’t every atom, ion, and molecule special in some way? Well, yes, but phosphate is uniquely constituted to provide services in the critical area of genetic information keeping and functional group transformation (without Pd and boronic acids).
Here is the curious thing: Biochemical systems use phosphorylation and hydrolysis as a means of executing molecular transformation. Remember oxidative phosphorylation? So, how is it that a phosphate moiety that is so useful as a leaving group or activator is also able to hold together DNA with such high fidelity?
In his much referenced 1987 paper entitled “Why Nature Chose Phosphates” (1), Frank Westheimer observed that phosphate diesters have a very useful property as a linking group for nucleic acids. The charged oxygen on (RO)2P(=O)O- serves several purposes. The presence of a charged linker renders DNA and RNA compatible with the hydrophilic environment inside the cell. The charge prevents the nucleic acid polymers from migrating to more hydrophobic environments found inside of cell membranes. And equally important, the monobasic anion serves as a kinetic barrier protecting the millions of phosphate linkages in a DNA strand from cleavage under neutral or basic hydrolytic conditions over the lifetime of the organism.
The hydrolytic stability of phosphate diesters is not to be underestimated. Westheimer points out that dimethylphosphate anion has a half life of 1 day at 110 C in 1 N base. He cites the rate constants at 35 C for the saponification of (CH3O)2PO2- is 2.0 E-9 (1/mol sec); (CH3O)3P=O is 3.4 E-4 (1/mol sec); and for ethyl acetate 1.0 E-2 (1/mol sec).
However, the very simplicity and current prevalence of phosphate ion in the environment does not go far in explaining how phosphate might have found its way into metabolic and structural use. In prebiotic times, the occurence of phosphate is in doubt (2). But not just the occurence of phosphate is in doubt. The relative abiotic inertness of phosphate towards esterification and the formation of other metabolically useful species raises the question of the original oxidation state of phosphorus during the onset of early life.
While phosphate is found in certain meteorites, Pasek suggests that a more ubiquitous meteoric phosphide mineral species such as schreibersite, (Fe, Ni)3P, found in iron meteorites may have provided the necessary reactive precursors for metabolic evolution (2). Pasek cites growing evidence of a late meteoric bombardment period at 3.8-3.9 GA.
Schreibersite hydrolyzes to a variety of oxidized species including phosphite. Phosphite has the advantage of being substantially more water soluble than phosphate, providing a larger molar concentration in seawater. Schreibersite reacts with acetate to form acetylphosphonate. In fact, a variety of organophosphorus compounds may be formed on exposure of schreibersite and its hydrolysis products with organic materials.
Lowly phosphate isn’t sexy like the newer anions triflate and BArF. But its seemingly mundane properties are key to the function of metabolism and genetics.
(1) F.H. Westheimer, Science, 1987, 235(4793), 1173-1178. (2) Pasek, M.A. PNAS, January 22, 2008, vol 105, no. 3, 853-858.