Carbonic acid H2CO3 (CA) is a key constituent of the universal CA/bicarbonate/CO2 buffer maintaining the pH of both blood and the oceans. Here we demonstrate the ability of intact CA to quantitatively protonate bases with biologically-relevant pKas and argue that CA has a previously unappreciated function as a major source of protons in blood plasma. We determine with high precision the temperature dependence of pKa(CA), pKa(T) = −373.604 + 16,500/T + 56.478 ln T. At physiological-like conditions pKa(CA) = 3.45 (I = 0.15 M, 37 °C), making CA stronger than lactic acid. We further demonstrate experimentally that CA decomposition to H2O and CO2 does not impair its ability to act as an ordinary carboxylic acid and to efficiently protonate physiological-like bases. The consequences of this conclusion are far reaching for human physiology and marine biology. While CA is somewhat less reactive than (H+)aq, it is more than 1 order of magnitude more abundant than (H+)aq in the blood plasma and in the oceans. In particular, CA is about 70× more abundant than (H+)aq in the blood plasma, where we argue that its overall protonation efficiency is 10 to 20× greater than that of (H+)aq, often considered to be the major protonating agent there. CA should thus function as a major source for fast in vivo acid–base reactivity in the blood plasma, possibly penetrating intact into membranes and significantly helping to compensate for (H+)aq’s kinetic deficiency in sustaining the large proton fluxes that are vital for metabolic processes and rapid enzymatic reactions.
In separate contributions, we have focussed on demonstrating that carbonic acid (CA) - historically considered too unstable to be a viable protonating agent - is able to protonate several types of pH indicators while behaving as a regular, moderately strong, carboxylic acid. Together with the experimental support we found for considering CA as a regular carboxylic acid are theoretical calculations demonstrating CA’s ability to protonate methylamine within 25 fs when forming with it a contact reactive complex. Here we briefly discuss a further aspect of this focus, involving the measurement of the lifetime and pKa of CA in pure methanol. The lifetime in methanol was found to be about 12-fold longer than in water, showing that the decomposition reaction of CA is solvent-dependent. The pKa change upon transferring CA from water to methanol was found to be 4.7 ± 0.1 pKa units, changing from 3.49 ± 0.03 to 8.16 ± 0.05: this change is similar to the pKa change observed for common stable carboxylic acids when these are transferred from water to methanol. These results add further support of our earlier proposal that CA can be an important protonating agent of biological bases in the blood plasma.
We locally probe with picosecond N K-edge spectroscopy electronic structure changes along all stages of the Förster photocycle of a prototypical photoacid, and determine how photoacid behaviour is driven by the conjugate photobase side.
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