A specific role of magnetic isotopes in biological and ecological systems. Physics and biophysics beyond.

The great diversity of molecular processes in chemistry, physics, and biology exhibits universal property: they are controlled by powerful factor, angular momentum. Conservation of angular momentum (electron spin) is a fundamental and universal principle: all molecular processes are spin selective, they are allowed only for those spin states of reactants whose total spin is identical to that of products. Magnetic catalysis induced by magnetic interactions is a powerful and universal means to overcome spin prohibition and to control physical, chemical and biochemical processes. Contributing almost nothing in total energy, being negligibly small, magnetic interactions are the only ones which are able to change electron spin of reactants and switch over the processes between spin-allowed and spin-forbidden channels, controlling pathways and chemical reactivity in molecular processes. The main source of magnetic and electromagnetic effects in biological systems is now generally accepted and demonstrated in this paper to be radical pair mechanism which implies pairwise generation of radicals in biochemical reactions. This mechanism was convincingly established for enzymatic adenosine triphosphate (ATP) and desoxynucleic acid (DNA) synthesis by using catalyzing metal ions with magnetic nuclei (25Mg, 43Ca, 67Zn) and supported by magnetic field effects on these reactions. The mechanism, is shown to function in medicine as a medical remedy or technology (trans-cranial magnetic stimulation, nuclear magnetic control of the ATP synthesis in heart muscle, the killing of cancer cells by suppression of DNA synthesis). However, the majority of magnetic effects in biology remain to be irreproducible, contradictory, and enigmatic. Three sources of such a state are shown in this paper to be: the presence of paramagnetic metal ions as a component of enzymatic site or as an impurity in an uncontrollable amount; the property of the radical pair mechanism to function at a rather high concentration of catalyzing metal ions, when at least two ions enter into the catalytic site; and the kinetic restrictions, which imply compatibility of chemical and spin dynamics in radical pair. The purpose of the paper is to analyze the reliable sources of magnetic effects, to elucidate the reasons of their inconsistency, to show how and at what conditions magnetic effects exhibit themselves and how they may be controlled, switched on and off, taking into account not only biological and madical but some geophysical and environmental aspects as well.

Nuclear spin selectivity in enzymatic catalysis: A caution for applied biophysics.

Nuclear magnetic ions 25Mg2+, 43Ca2+, and 67Zn2+ suppress DNA synthesis by 3-5 times with respect to ions with nonmagnetic nuclei. This observation unambiguously evidences that the DNA synthesis occurs by radical pair mechanism, which is well known in chemistry and implies pairwise generation of radicals by electron transfer between reaction partners. This mechanism coexists with generally accepted nucleophilic one; it is switched on, when at least two ions enter into the catalytic site. It is induced by both sorts of ions, magnetic and nonmagnetic but it functions by 3-5 times more efficiently with magnetic ions stimulating radical pair mechanism. Decreasing catalytic activity of polymerases by 3-5 times, nuclear magnetic ions 25Mg2+, 43Ca2+, and 67Zn2+ even more strongly, by 30-50 times, increase mortality of cancer cells. The two reasons of this unique phenomenon are suggested: first, the high concentration of nuclear magnetic ions delivered by specific nano-container into the cancer cells, and, second, generation of short DNA fragments by polymerases loaded with nuclear magnetic ions, which is known to activate protein p53, efficiently stimulating apoptosis of cancer cells.

Ultrashort ssDNA in Retinoblastoma Patients Blood Plasma Detected by a Novel High Resolution HPLC Technique: a Preliminary Report.

A significant population of ultrashort (50-150n) single-stranded DNA fragments were found in exosome-free blood plasma of retinoblastoma patients (6.84 ng mL-1), but not in plasma of healthy donors. An original high resolution HPLC technique has been proposed to reveal and characterize this peculiarity. To solve this task, a novel molecular size exclusion - anion exchange analytical technique was developed. Its applicability to diagnostics and oncogenesis research is quizzed here.

Retinoblastoma: Magnetic Isotope Effects Might Make a Difference in the Current Anti-Cancer Research Strategy.

Human retinoblastoma cells were proven to possess some very unusual DNApolß species. Being 23.5 kDa monomers, which itself is not common for the DNApolß superfamily members, these chromatin associated proteins manifests most of the DNApolß-specifc functional peculiarities making them legitimate targets for DNA repair cytostatic inhibitors. Particularly, these tumor specific enzymes were found to be very sensitive to 25Mg2+-, 43Ca2+- and 67Zn2+-promoted magnetic isotope effects (MIE) caused a marked DNA sequence growth limitation as well as a formation of the size-invalid, i.e. too short in length, DNA fragments, totally inappropriate for the DNA repair purpose. This MIE-DNApolß match may serve a starting point for further move towards the paramagnetic path in current developments of anti-cancer strategies.