Abstract The role of proton tunnelling in biological catalysis is investigated here within the frameworks of quantum information theory and thermodynamics. We consider the quantum correlations generated through two hydrogen bonds between a substrate and a prototypical enzyme that first catalyses the tautomerization of the substrate to move on to a subsequent catalysis, and discuss how the enzyme can derive its catalytic potency from these correlations. In particular, we show that classical changes induced in the binding site of the enzyme spreads the quantum correlations among all of the four hydrogen-bonded atoms thanks to the directionality of hydrogen bonds. If the enzyme rapidly returns to its initial state after the binding stage, the substrate ends in a new transition state corresponding to a quantum superposition. Open quantum system dynamics can then naturally drive the reaction in the forward direction from the major tautomeric form to the minor tautomeric form without needing any additional catalytic activity. We find that in this scenario the enzyme lowers the activation energy so much that there is no energy barrier left in the tautomerization, even if the quantum correlations quickly decay.
Abstract The role of proton tunnelling in biological catalysis is investigated here within the frameworks of quantum information theory and thermodynamics. We consider the quantum correlations generated through two hydrogen bonds between a substrate and a prototypical enzyme that first catalyses the tautomerization of the substrate to move on to a subsequent catalysis, and discuss how the enzyme can derive its catalytic potency from these correlations. In particular, we show that classical changes induced in the binding site of the enzyme spreads the quantum correlations among all of the four hydrogen-bonded atoms thanks to the directionality of hydrogen bonds. If the enzyme rapidly returns to its initial state after the binding stage, the substrate ends in a new transition state corresponding to a quantum superposition. Open quantum system dynamics can then naturally drive the reaction in the forward direction from the major tautomeric form to the minor tautomeric form without needing any additional catalytic activity. We find that in this scenario the enzyme lowers the activation energy so much that there is no energy barrier left in the tautomerization, even if the quantum correlations quickly decay.
• A study published in the international journal Communications Physics demonstrated the phenomenon of proton tunneling inside DNA utilizing an open quantum systems approach. • The research confirmed that protons within DNA hydrogen bonds pass through binding barriers via quantum tunnelling, going well beyond simple thermal fluctuations, and that this plays a dominant role in the conversion of base pairs into rare tautomers. • This is a groundbreaking result proving that the fundamental genetic mutation process of life is driven by microscopic quantum tunneling probabilities, revealing that tautomeric states can induce natural point mutations. [Quantum Biology Society] The DNA double helix, which contains all the genetic information of living organisms, is stably maintained by hydrogen bonds between base pairs. However, even in this robust structure, unexplained point mutations occasionally occur, becoming the seeds of evolution and disease. Recently, a study demonstrating that quantum tunnelling—a bizarre physical law of the subatomic world—is deeply involved behind this fundamental biological phenomenon was published, surprising both the biology and physics communities. The paper detailing this groundbreaking discovery, titled "An open quantum systems approach to proton tunnelling in DNA," was made freely available in Communications Physics, a sister journal to the world-renowned Nature. A research team consisting of Louie Slocombe, Marco Sacchi, and Jim Al-Khalili from the University of Surrey in the UK led this interdisciplinary study. ■ The Power of Quantum Tunneling Beyond Classical Chemistry From the perspective of general classical biochemistry, it has been assumed that for protons forming DNA hydrogen bonds to change positions, sufficient thermal fluctuation is required to overcome the binding barrier. However, the researchers discovered a surprising fact through an open quantum systems model that precisely reflects the effects of decoherence and dissipation within the cellular environment. Protons instantly change their binding positions through quantum tunneling, passing through the barrier despite a lack of energy, and the contribution of quantum tunneling to the chemical reaction rate is several orders of magnitude larger than classical over-the-barrier hopping. ■ The Beginning of Mutation: Tautomeric Conversion According to the analysis, this quantum tunneling plays a dominant role in the conversion of Guanine-Cytosine (G-C) base pairs from their canonical form into highly rare and unstable tautomeric forms. The problem arises when the DNA strands are separated by the helicase enzyme and replication occurs in this state. The research team confirmed that at biological temperatures (around 300K), the thermal equilibrium occupation probability of the tautomer reaches an astoundingly high value of 1.73 × 10⁻⁴. This is significantly higher than the previously known natural spontaneous mutation rate (about 10⁻⁸), strongly suggesting that tautomerisation via quantum tunneling is a substantial and crucial cause of point mutations. ■ Presenting a New Paradigm in Life Sciences This study is a monumental achievement proving that genetic stability and the mutation process—the most fundamental and secretive domain of life—are not accidental chemical mistakes but are directly driven by the probability of quantum tunneling, a physical law of the microscopic world. This is a powerful demonstration that overturns the conventional view of interpreting biological phenomena solely through macroscopic molecular structures and chemical bonds, showing that quantum mechanics can be the key to fully explaining genetic mutation models.
Quantum tunneling events occurring through biochemical bonds are capable of generating quantum correlations between bonded systems, which in turn makes the conventional second law of thermodynamics approach insufficient to investigate these systems. This means that the utilization of these correlations in their biological functions could give an evolutionary advantage to biomolecules to an extent beyond the predictions of molecular biology that are generally based on the second law in its standard form. To explore this possibility, we first compare the tunneling assisted quantum entanglement shared in the ground states of covalent and hydrogen bonds. Only the latter appears to be useful from a quantum information point of view. Also, significant amounts of quantum entanglement can be found in the thermal state of hydrogen bond. Then, we focus on an illustrative example of ligand binding in which a receptor protein or an enzyme is restricted to recognize its ligands using the same set of proton-acceptors and donors residing on its binding site. In particular, we show that such a biomolecule can discriminate between [Formula: see text] agonist ligands if it uses the entanglement shared in [Formula: see text] intermolecular hydrogen bonds as a resource in molecular recognition. Finally, we consider the molecular recognition events encountered in both the contemporary genetic machinery and its hypothetical primordial ancestor in pre-DNA world, and discuss whether there may have been a place for the utilization of quantum entanglement in the evolutionary history of this system.
Abstract Context Proton transfer in drug–protein cavities is central to enzymatic catalysis and pH-responsive drug delivery, yet classical models often fail to capture the quantum mechanical behavior that governs these processes. The influence of nanoscale confinement on proton dynamics through quantum effects remains poorly understood, limiting our ability to design optimized therapeutic systems. We present a quantum theoretical framework that connects cavity geometry with measurable proton transfer properties, offering new insights for biocatalysis and nanomedicine. Method We developed an analytical model for proton confinement in biological cavities by solving the Schrödinger equation for two spherically symmetric potentials: finite square wells representing hydrophobic environments and Morse potentials for hydrogen-bonded systems. Our approach systematically calculates ground-state energies, wavefunctions, tunneling probabilities, and vibrational overtones. Results show confinement geometry exponentially modulates proton behavior, with tunneling probabilities spanning > 12 orders of magnitude under physiological conditions. Kinetic isotope effects (> 10¹¹) and catalytic enhancements (10³-fold) confirm quantum tunneling dominance. While finite wells promote classical localization, Morse potentials enable efficient proton transfer through delocalization. The model incorporates environmental decoherence and establishes design rules linking cavity parameters to spectroscopic and kinetic signatures, providing a bridge between quantum theory and structural biology.
Abstract We review recent studies of the interconversion mechanism of OH···O hydrogen-bonded centrosymmetric dimers through proton transfer in the prototype crystals of potassium hydrogen carbonate (KHCO3) and benzoic acid (C6H5COOH). The point at issue is whether the proton distributions at various temperatures arise from classical statistical mixtures of tautomers or quantum mechanical superposition states. A related issue is whether it is possible to probe a quantum superposition without inducing decoherence and classicality. We show that neutron diffraction can realize decoherence-free measurements for strictly defined scattering geometries and thus evidence macroscopic quantum correlations. We present a theoretical framework for decoherence-free macroscopically entangled states of the sublattice of protons. The neutron diffraction cross-section of protons is enhanced by a factor of ~45, compared to regular Bragg diffraction, and quantum correlations are observed with remarkable contrast. At elevated temperatures, up to 300 K, quantum correlations are unaffected by proton transfer. The crystal is a coherent superposition of macroscopic tunnelling states, like Schrödinger's cat in a superposition of dead and alive states.
The traditional understanding of chemical catalysis heavily relies on classical transition state theory and potential energy surface modification, treating reactions as stochastic processes driven by random thermal collisions. This paper introduces the Molecular Entanglement Catalysis Theory (MECT), a paradigm-shifting framework that transcends the classical energy-barrier model. MECT posits that high catalytic efficiency is achieved not merely through static energy reduction, but via the active alteration of reaction information transmission modality through quantum entanglement. By establishing non-local quantum correlations between the catalyst and the substrate, the system bypasses classical statistical limitations. We construct a comprehensive mathematical framework incorporating total system Hamiltonians, Lindblad master equations for open quantum systems, and quantum mutual information to track the evolution of the density matrix. The theory demonstrates that the quantum mutual information I(C:S) acts as an informational conduit that actively guides the reactant wavefunction toward the product state configuration, effectively lowering the quantum informational free energy change expressed as Delta_G_quantum = Delta_G_classical - k_B * T * I(C:S). This framework provides profound insights into biological enzymatic efficiency, such as allosteric regulation and ambient bond cleavage, and paves the way for designing next-generation synthetic catalysts engineered for quantum coherence and information-driven reaction control.
We build on our earlier quantum wavepacket study of hydrogen transfer in the biological enzyme, soybean lipoxygenase-1, by using von Neumann quantum measurement theory to gain qualitative insights into the transfer event. We treat the enzyme active site as a measurement device which acts on the tunneling hydrogen nucleus via the potential it exerts at each configuration. A series of changing active site geometries during the tunneling process effects a sequential projection of the initial, reactant state onto the final, product state. We study this process using several different kinds of von Neumann measurements and show how a discrete sequence of such measurements not only progressively increases the projection of the hydrogen nuclear wavepacket onto the product side but also favors proton over deuteron transfer. Several qualitative features of the hydrogen tunneling problem found in wavepacket dynamics studies are also recovered here. These include the shift in the "transition state" towards the reactant as a result of nuclear quantization, greater participation of excited states in the case of deuterium, and presence of critical points along the reaction coordinate that facilitate hydrogen and deuterium transfer and coincide with surface crossings. To further "tailor" the dynamics, we construct a perturbation to the sequence of measurements, that is a perturbation to the dynamical sequence of active site geometry evolution, which leads us to insight on the existence of sensitive regions of the reaction profile where subtle changes to the dynamics of the active site can have an effect on the hydrogen and deuterium transfer process.