Quantum Energetics in the Differential Dynamics of Transient mRNA versus Stable DNA

While RNA’s 2′ hydroxyl group has long been recognized as a primary contributor to mRNA instability, owing to its heightened susceptibility to hydrolytic cleavage, this manuscript introduces a complementary quantum-biological hypothesis. It explores how vibrational modes, quantum coherence, and electromagnetic coupling influence nucleotide behavior through dynamic, real-time quantized boundary formation, governed by conservation principles such as E = mc2 and E = hf. Crucially, protonation states modulated by pKa transitions amplify local energy fluctuations, fostering transient configurations in mRNA. These instabilities are further shaped by van der Waals (vdW) interactions and the anisotropic nature of three-dimensional molecular geometry, which modulate proximity-dependent quantum effects in a context-sensitive manner. Drawing inspiration from Bohm’s implicate order, the study proposes that mRNA’s transience reflects a divergent conformational landscape, continuously perturbed by quantum-level variability. In contrast, DNA’s relative resilience is attributed to its helical architecture and robust repair mechanisms. Building on this framework, the manuscript challenges conventional paradigms by advancing a quantum-biological model to explain both the inherent instability of natural mRNA and the enhanced stability of its N1-methylpseudouridine (m1Ψ)-modified variant. It reconceptualizes nucleotide resilience through the lens of vibrational dynamics, quantum coherence, and electromagnetic interactions, integrated with classical physical principles. The study further investigates how m1Ψ influences polarity, folding, and base stacking in therapeutic mRNA. Although structurally analogous to thymidine in DNA rather than uridine, m1Ψ does not achieve full energetic equivalence. The central hypothesis, bridging quantum physics and molecular biology, is that m1Ψ must confer stabilizing effects comparable to thymidine, mitigating quantum-scale fluctuations through emergent structural coherence. The pivotal question remains: is N1-methylpseudouridine a functionally equivalent substitute for uridine in therapeutic contexts?