Intrinsic Hydrogen Bond Asymmetry as a Determinant of Hydration Shell Structure in DNA and Electrical Coherence

Two experimental findings, established independently and not previously considered together, are proposed to intersect in the ordered water of the DNA double helix. First, hygroscopic biological materials constitute a distinct class of matter, hydration solids, whose mechanics are governed by the hydration force acting within nanoscale pores (Harrellson et al., 2023). Second, water molecules are intrinsically asymmetric hydrogen-bond donors, maintaining one strong and one weak bond with anti-correlated strengths refreshed on sub-picosecond timescales (Gunkel et al., 2024). This paper proposes that the DNA hydration shell is a hydration solid, and that molecular bond asymmetry contributes to determining the ordering and exchange dynamics of its first-shell water. Within the minor groove, a water molecule presenting one strong and one weak donor bond to chemically inequivalent acceptor sites, anionic phosphate oxygens and base-edge heteroatoms, adopts orientations matched to or frustrated against the available geometry, with consequences for the stable occupation of hydration positions and the tempo of rearrangement. The hydrogen bond is also an electrical structure: it shares electrons, it carries charge along its chains, and DNA conducts only when hydrated. The paper proposes that the asymmetric shell is part of DNA's electrical pathway, which ties the structure of the shell to the electrical signature of damaged DNA. Four experiments are proposed, each executable with existing methods: isotopic substitution monitored by chiral sum-frequency generation spectroscopy, counterion and temperature perturbation studies, sequence-dependent comparison of shell observables, and isotope-dependent DNA charge transport. The paper is an exercise in field synthesis: the identification of connections between published results across compartmentalized disciplines, presented for evaluation by researchers in the relevant domains.