The Proton in Biochemistry: Impacts on Bioenergetics, Biophysical Chemistry, and Bioorganic Chemistry

The proton is the smallest atomic particle, and in aqueous solution it is the smallest hydrated ion, having only two waters in its first hydration shell. In this article we survey key aspects of the proton in chemistry and biochemistry, starting with the definitions of pH and pKa and their application inside biological cells. This includes an exploration of pH in nanoscale spaces, distinguishing between bulk and interfacial phases. We survey the Eigen and Zundel models of the structure of the hydrated proton, and how these can be used to explain: a) the behavior of protons at the water-hydrophobic interface, and b) the extraordinarily high mobility of protons in bulk water via Grotthuss hopping, and inside proteins via proton wires. Lastly, we survey key aspects of the effect of proton concentration and proton transfer on biochemical reactions including ligand binding and enzyme catalysis, as well as pH effects on biochemical thermodynamics, including the Chemiosmotic Theory. We find, for example, that the spontaneity of ATP hydrolysis at pH ≥ 7 is not due to any inherent property of ATP (or ADP or phosphate), but rather to the low concentration of H+. Additionally, we show that acidification due to fermentation does not derive from the organic acid waste products, but rather from the proton produced by ATP hydrolysis.

Signature of the Surface Hydrated Proton and Associated Restructuring of Water at the Model Membrane Interfaces: Vibrational Sum Frequency Generation Study

Hydrated proton at the membrane interface plays an important role in the bioenergetic process of mostly all organisms. Herein, the signature of the hydrated proton at the membrane interfaces has...

DNA Nucleobase Under Ionizing Radiation: Unexpected Proton Transfer by Thymine Cation in Water Nanodroplets

<p>The effects of ionizing radiation on DNA constituents is a widely studied fundamental process using experimental and computational techniques. In particular radiation effects on nucleobases are usually tackled by mass spectrometry in which the nucleobase is embedded in a water nanodroplet. Here we present a multiscale theoretical study revealing the effects and the dynamics of water droplets towards neutral and ionized thymine. In particular, by using both hybrid quantum mechanics/ molecular mechanics and fully ab initio molecular dynamics we reveal an unexpected proton transfer from thymine cation to a nearby water molecule. This leads to the formation of a neutral radical thymine and a Zundel structure, while the hydrated proton localizes at the interface between the deprotonated thymine and the water droplet. This observation opens entirely novel perspective concerning the reactivity and further fragmentation of ionized nucleobases.</p>

DNA Nucleobase Under Ionizing Radiation: Unexpected Proton Transfer by Thymine Cation in Water Nanodroplets

<p>The effects of ionizing radiation on DNA constituents is a widely studied fundamental process using experimental and computational techniques. In particular radiation effects on nucleobases are usually tackled by mass spectrometry in which the nucleobase is embedded in a water nanodroplet. Here we present a multiscale theoretical study revealing the effects and the dynamics of water droplets towards neutral and ionized thymine. In particular, by using both hybrid quantum mechanics/ molecular mechanics and fully ab initio molecular dynamics we reveal an unexpected proton transfer from thymine cation to a nearby water molecule. This leads to the formation of a neutral radical thymine and a Zundel structure, while the hydrated proton localizes at the interface between the deprotonated thymine and the water droplet. This observation opens entirely novel perspective concerning the reactivity and further fragmentation of ionized nucleobases.</p>

Nature of hydrated proton vibrations revealed by nonlinear spectroscopy of acid water nanodroplets

Using polarization-resolved pump–probe spectroscopy we find that hydrated protons have two different OH-stretch vibrations, which are due to asymmetry of the hydration structure.