A Multiscale Computational Framework for the Mg-28 Radio-Cofactor Hypothesis: Conditional Emergence of Coordinated Disruption under the Gate Condition

Abstract

Cancer therapy continues to confront molecular redundancy, metabolic plasticity and multiscale adaptability that limit durable responses. Most existing modalities act on downstream products, signaling pathways or extracellular recognition structures, while the deeper intracellular regulatory architecture that sustains malignant proliferation remains comparatively underexplored. Enzymatic cofactors occupy a uniquely fundamental position within this architecture: they enable catalytic activity itself. The Radio-Cofactor Hypothesis proposes that an essential biological cofactor can serve as an endogenous carrier of radionuclide activity. Using magnesium-28 (28Mg) as prototype, the hypothesis posits that a radioactive isotope chemically indistinguishable from physiological Mg2+ can occupy magnesium-dependent catalytic sites; subsequent nuclear transformation then generates simultaneous alteration of cofactor identity and highly localized energy deposition within the active site. The present study does not experimentally demonstrate catalytic-site occupancy. Instead it treats non-zero fractional occupancy ({theta}28 > 0) as an explicit input premise--the Gate Condition--and constructs a hierarchical computational discovery platform that integrates nuclear-decay physics, magnesium enzymology, intracellular transport, mitochondrial and nuclear responses, radiobiology, pharmacokinetics and tumor-growth dynamics. Information propagates across six organizational levels according to defined bottom-up and top-down rules. Under the gate-condition assumption the framework generates a sequence of emergent behaviors: the Atomic Switch / Decay-Induced Octahedral Collapse at the molecular scale, progressive Enzyme Disruption Index (EDI) across functional enzyme classes, a coordinated Quadruple-Kill cascade linking catalytic, radiolytic, mitochondrial and transcriptional injury, and a system-level Quintax Functional Model. Tissue-scale trajectories are described by an intrinsic Gompertz formulation, while whole-body dosimetry is evaluated against QUANTEC constraints. All higher-scale predictions remain strictly conditional upon satisfaction of the gate condition and upon the phenomenological transport and uptake parameters assigned to the model. The framework is therefore hypothesis-generating rather than predictive of clinical efficacy. Its principal contribution is to convert the radio-cofactor concept into a quantitatively linked, experimentally addressable cascade and to provide a clear roadmap of decision points--beginning with verification of differential magnesium transport and catalytic-site occupancy --for systematic empirical interrogation.