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. 2023 Oct 21;15(5):999–1006. doi: 10.1007/s12551-023-01162-6

Magnetic isotope effects and nuclear spin catalysis in living cells and biomolecular motors: recent advances and future outlooks

Nuclear spin catalysis

Vitaly K Koltover 1,✉
PMCID: PMC10643427  PMID: 37974974

Abstract

Biomolecular nanoreactors are constructed from chemical elements many of which have magnetic and nonmagnetic stable isotopes. The magnetic isotope effects (MIE) were discovered in experiments with the cells enriched with different isotopes of magnesium, magnetic or nonmagnetic ones. The striking catalytic effect of the magnetic isotope, 25Mg, was revealed in the reaction of ATP hydrolysis driven by myosin, the biomolecular motor utilizing the chemical energy of ATP to perform the mechanical work. The rate of the enzymatic ATP hydrolysis with 25Mg as the enzyme cofactor is twice higher than the rates of the reactions with nonmagnetic 24Mg or 26Mg. A similar effect of the nuclear spin catalysis was revealed in the experiments with zinc as the myosin cofactor. MIE unambiguously indicate that, in the chemo-mechanical process catalyzed by the molecular motor, there is a limiting step which depends on the electron spin state of the reagents, and this step is accelerated by the nuclear spin of the magnetic isotope. The recent developments in this field highlight promising venues for future research of MIE in biophysics with possible applications of the magnetic isotopes in medical physics including radiation medicine and biomedical effects of electromagnetic fields.

Keywords: Nuclear spin catalysis, Magnetic isotopes, Biomolecular motors, Myosin, ATP, Reliability of biomolecular nanoreactors

Introduction

All biomolecular nanoreactors and other cell components are constructed from atoms of chemical elements. Some of the elements have magnetic and nonmagnetic stable isotopes. Meanwhile, atomic nuclei of some magnetic isotopes create local magnetic fields, at a distance of chemical bond length, 10–100 times greater than the terrestrial field, the strength of which is about 0.05 mT (Grant and Harris 1996). In chemical physics, magnetic isotope effects (MIE) are known for a long time for a long list of elements including carbon, oxygen, silicon, sulfur, germanium, tin, mercury, and even uranium (Buchachenko et al. 1978; Brocklenhurst 2002; Turro 1983; Zeldovich et al. 1988). In biological physics, accordingly, the question arises whether the magnetic fields of the atomic nuclei impact the efficiency and reliability of the operation of biomolecular nanoreactors or, in other words, whether living cells can perceive the difference between magnetic and nonmagnetic nuclei of the same element?

This paper is a brief review of the works in which MIE in living cells and the nuclear spin catalysis effects in molecular motors of cell bioenergetics were discovered. The paper is based on the materials of the lecture presented at VII Congress of Russian Biophysicists, 17–23 April 2023, Krasnodar City, Russia.

Magnetic isotope effects in biophysics

Magnetic isotope effects in living cells

Magnesium (Mg) is of special interest in searching for MIE in living nature. It is generally known that cations of magnesium, Mg2+, serve the obligate cofactor functions for about three hundred enzyme reactions, including DNA- and RNA-polymerases and enzymes for synthesis and hydrolysis of ATP, among them—myosin and other “molecular motors” of cell bioenergetics. There are three stable isotopes of magnesium, 24Mg, 25Mg, and 26Mg with a natural abundance of approximately 78.7, 10.13, and 11.17%. Only 25Mg has the nuclear spin (I = 5/2) and, as a consequence, it is the magnetic isotope, while 24Mg and 26Mg are spinless (I = 0) and, as a consequence, these isotopes are nonmagnetic ones (Grant and Harris 1996).

The first attempts to detect MIE in biochemistry have been taken in experiments with mitochondria isolated from mouse hearts. It was found that ATP synthesis at oxidative phosphorylation with 25Mg proceeds 2–3 times faster than that with nonmagnetic 24Mg or 26Mg (Buchachenko et al. 2005). The experiments were initiated by the hypothesis about the key role of the virtual radical-ion pair in the synthesis of ATP at oxidative phosphorylation (Blumenfeld and Koltover 1972). Since the nonmagnetic magnesium isotopes, 24Mg (78.7%) and 26Mg (11.17%), are the most abundant in nature, cells and tissues mostly contain the nonmagnetic isotopes, viz. 89.87%. To solve this problem, the authors of the cited paper had first removed natural magnesium from mitochondria, using the chelator, EGTA, and then they added magnesium chloride of the desired isotope into the mitochondria, thus treated (Buchachenko et al. 2005). Meanwhile, with such treatment, it is impossible to avoid undesirable structural and functional changes in mitochondria (Nohl et al. 1993). Furthermore, the same group has reported that the magnetic ions 25Mg2+, 67Zn2+, and 43Ca2+ increase, 30–50 times, the mortality of cancer cells (see refs. in Buchachenko et al. 2020). In cells and tissues, however, the natural contents of the magnetic isotopes of 25Mg, 67Zn, and 43Ca are, correspondingly, 10.13%, 4.1%, and 0.145%. Correspondingly, there is no certainty that the cited effects of increased mortality of the cancer cells were precisely caused by the magnetic isotopes and were not caused by admixtures of toxic trace elements with which the isotope preparations were contaminated. Unfortunately, there are no data of mass spectrometry or atomic emission spectrometry concerning the element compositions of the cell media in the cited papers.

Inasmuch as cells and tissues mostly contain the nonmagnetic isotopes of magnesium, there is only one single way to achieve reliable results in the search for MIE, namely—experiments with cells enriched with different isotopes of magnesium, magnetic or nonmagnetic ones. The first experiments in this way were performed with cells of the bacteria Escherichia coli (Bogatyrenko et al. 2009; Koltover 2010, 2012; Koltover et al. 2012b). The degree of enrichment of the cells with the required magnesium isotope was about 80 percent. It was revealed that the bacterial cells essentially faster adapt to the growth media, enriched with 25Mg, by comparison with their adaptation to the media, enriched with nonmagnetic 24Mg or 26Mg. Besides, the colony-forming ability of the cells, which were previously grown on 25Mg, was essentially higher in comparison with the cells grown on the nonmagnetic magnesium isotopes. Moreover, it was found that the activity of superoxide dismutase, an important antioxidant enzyme, in the cells which were grown on 25Mg was essentially lower, 40–50%, than the activity of this enzyme in the cells grown on the nonmagnetic 24Mg or Mg of the natural isotope composition (Bogatyrenko et al. 2009; Koltover 2010).

In parallel, MIE of 25Mg were revealed in experiments with another commonly accepted cell model, the yeast Saccharomyces cerevisiae (Koltover et al. 2012a; Koltover et al. 2013; Avdeeva et al. 2019; Koltover 2019). The experiments were performed in collaboration with the Department of Radiation Biology of the Institute of Cell Biology and Genetic Engineering, NAS, Kyiv, and the Department of Molecular and Radiation Biophysics of Petersburg Institute of Nuclear Physics (NRC “Kurchatov Institute”), Gatchina, Leningrad Region. The cells were grown on standard media supplied with different isotopes of magnesium and were enriched, up to 80–90%, with the relevant magnesium isotope. The magnesium isotopic compositions in the solutions were determined and controlled by the inductively coupled plasma mass spectrometry (ICP-MS) method. Elemental compositions of the solutions, including contents of impurities, were determined by the ICP-MS method and the inductively coupled plasma atomic emission spectroscopy (ICP-AES).

The cells enriched with different magnesium isotopes were irradiated by short-wave UV light (240–260 nm) or by the gamma-rays (60Co, dose 300 Gy). Thereafter, the kinetics of post-radiation recovery of the cells, irradiated by UV light, and the kinetics of post-radiation recovery of the cells, irradiated by ionizing radiation, in the nutrient-free (“starving”) media were studied. The experiments on the UV-irradiated cells were carried out five times with the cells enriched with each kind of magnesium isotope. The experiments on the gamma-irradiated cells were carried out four times with each kind of magnesium isotope. Survival of the cells transferred to a nutrient medium (agar) immediately after irradiation do not exceed a few percent because most of the cells do not have enough time to repair their damaged genetic structures before mitosis and, as a result, nonviable daughter cells are produced at the cell division. Incubation in the “starving” media, in which the cells do not divide, provides them with additional time for repair processes and, consequently, leads to an increase in survival. It was revealed that the cells enriched with the magnetic 25Mg are recovered more effectively than the cells enriched with the nonmagnetic 24Mg. In both cases, in experiments with UV radiation as well as in experiments with gamma radiation, the recovery rate constant was twice as high for the cells enriched with 25Mg than that for the cells enriched with 24Mg. Thus, MIE have been detected, i.e., acceleration of the post-radiation recovery of the cells by the magnetic isotope’s nuclear spin. Moreover, in the experiments with ionizing radiation, it was found that the fraction of the irreversible damages in the cells enriched with 25Mg was 50–60% less than in the cells enriched with 24Mg (Avdeeva et al. 2019). Besides, the effects of the external magnetic field, strength 60 mT, on the post-radiation recovery of the UV-irradiated yeast cells were studied. No effects were found in the experiments with the cells, enriched with 24Mg, while the beneficial effect was found in the experiments with the cells, enriched with 25Mg. Namely, the twofold acceleration of the post-radiation recovery rate of the cells, enriched with the magnetic magnesium isotope, has been revealed in the presence of the external magnetic field (Koltover et al. 2012a).

One might assume that the detected effects are really not the magnetic isotope effects but are caused by differences in the contents of impurities of other elements entering the growth media with different magnesium isotopes. However, according to the element analysis data, the compositions of the growth media, enriched with different magnesium isotopes, were the same in all samples and the contents of impurity elements were no more than a few micromoles per liter, regardless of the type of the magnesium isotope. Besides, it should be taken into account that not only magnesium, but also other reagents, which are necessary for the nutrient media, are contaminated with impurity elements. These elements enter the media in the same amounts, regardless of the type of magnesium, and, moreover, in the amounts significantly exceeding the amounts of the same impurities introduced with the magnesium isotopes.

Thus, in experiments with the cells irradiated with UV light as well as in the experiments with cells irradiated with ionizing radiation, the acceleration of post-radiation recovery of the cells by the magnesium magnetic isotope has been revealed, in essence, the nuclear spin catalysis.

The studies of the E. coli bacteria were continued by the Russian group at Orenburg State University (Letuta et al. 2017; Letuta and Berdinskiy 2019; Letuta 2021), Continuing our first collaborative research (Koltover et al. 2012b), they confirmed that the intracellular enrichment with the magnetic isotope, 25Mg, increases viability (colony-forming ability, CFU) of the cells, in particular, their resistance to antibiotics. Besides, this group studied the influence of external magnetic fields on the viability of the cells enriched with various isotopes of magnesium and zinc. It was found that the external magnetic fields, strength 70–95 mT, doubles the colony-forming ability of the cells, enriched with the magnetic 25Mg, but has little, if any, effect on the CFU of the cells, enriched with the nonmagnetic magnesium isotopes (Letuta et al. 2017; Letuta 2021). Here, it is appropriate to recall that a similar magnetic field effect was previously discovered in the experiments with isotope-enriched yeast cells (Koltover et al. 2012a). These authors have also reported about similar effects of external magnetic fields in combination with the magnetic isotope of zinc, 67Zn (Letuta and Berdinskiy 2019). These authors believe that the magnetosensitivity of cells is caused by the increase in the ATP synthesis at oxidative phosphorylation under the magnetic isotopes, referring noncritically onto the previous papers of their colleagues (Buchachenko et al. 2005, 2020). Besides, the cited papers are not provided with data on the degree of enrichment of the cells with the desired isotope, just as there are no data on the amount and elemental composition of impurities introduced into the growth medium with the isotopes. Meanwhile, the natural content of the magnetic zinc isotope is only 4.1%, which, taking into account the high cost of the isotopes, makes it hardly possible to enrich cells with this isotope.

Magnetic isotope effects in biomolecular motors

It is generally known that all adaptation processes, especially reparation from radiation damages, require energy. The main source of energy in cell bioenergetics is adenosine triphosphate (ATP). Reasoning from the common knowledge that Mg2+ serves the obligate cofactor functions for many enzymes, including the enzymes of bioenergetics (Grant and Harris 1996), it was reasonable to suggest that MIE discovered in the experiments with living cells are stemming from the higher efficiency of the bioenergetics processes in the cells, enriched with a magnetic isotope of magnesium.

The experiments in this direction have initially been performed with mitochondrial H+-ATPase (complex MF0F1) in the Institute of Physical Chemistry, University of Freiburg (Koltover et al. 2017). The enzyme was isolated from the mitochondria of yeast S. cerevisiae, and then it was incorporated (“reconstituted”) into the liposome membranes (“proteoliposomes”). The MF0F1 complex is generally considered the simplest enzyme construct for studying mechanisms of oxidative phosphorylation (Förster et al. 2010). In order to eliminate initial MgCl2 from the liposome complexes, they were pellet by centrifugation and then precipitated in standard reaction solutions supplemented with 24MgCl2, or 25MgCl2, or MgCl2 of natural isotope abundance. The enzyme activity was measured by the luciferin/luciferase assay at 25 °C. The reaction of ATP synthesis has been initiated by the standard technique of pH-jump, i.e., the acid-base transition from pH 5.4 to pH 8.0. As it turned out, no MIE were found in the ATP synthesis, neither at 2.5–4.0 mM of the magnesium chlorides (physiological concentrations) nor at 15 mM (high enough to replace the initial MgCl2 from the liposomes). However, a striking catalytic effect of the magnetic 25Mg was revealed in the reaction of hydrolysis of ATP. The rate of the ATP hydrolysis with magnetic 25Mg has turned out to be higher than the rates of the ATP hydrolysis with nonmagnetic 24Mg or Mg of natural isotope abundance at the same concentrations (15 mM). At this, the data of element analysis of the preparations by the methods of atomic emission spectrometry and mass spectrometry testified that the detected differences in the enzyme activity cannot be attributed to any impurity elements in the reaction solutions supplied with different isotopes of magnesium. Thus, we have detected the catalytic magnetic isotope effect (nuclear spin catalysis) in the enzymatic ATP hydrolysis driven by isolated mitochondrial H+-ATPase. The catalytic effect of 25Mg was small (20–30%) but statistically reliable at P ≤ 0.05 (Koltover et al. 2017).

Furthermore, similar experiments with myosin were performed in cooperation with the Department of Muscle Biochemistry of Palladin Institute of Biochemistry, NAS, Kyiv, Ukraine (Koltover et al. 2014, 2016, 2018, 2020). Myosin catalyzes the reaction of hydrolysis of the terminal phosphate bond in the ATP molecule: ATP + H2O ➔ ADP + Pi. The released energy, about 0.54 eV, is used to carry out the mechanical work, i.e., muscle contraction. We investigated the effects of the different magnesium isotopes, magnetic 25Mg, and nonmagnetic 24Mg and 26Mg, on the hydrolase activity of the catalytic fragment (subfragment-1) of myosin isolated from the myometrium muscle of pigs. Subfragment-1 is considered as the sufficient functional unit of myosin since it retains all native functional properties of myosin, namely ATPase activity and ability to interact with actin. Three independent series of experiments were performed for different myosin preparations isolated at different times from three different animals. The experiments for each of these preparations were repeated from three to eight times with each magnesium isotope at 37°C in the standard reaction solutions which contained 5 mM (physiological concentration) of 24MgCl2, 25MgCl2, 26MgCl2, or MgCl2 of natural isotope abundance. Regardless of the variability of the mean values of ATPase activity in the experimental series, the same MIE were observed in all the series. Namely, in the presence of the magnetic isotope, the initial rate of the enzyme ATP hydrolysis is 2–2.5 times higher than that for the same enzyme with the nonmagnetic isotope. Moreover, a similar catalytic effect was detected in the experiments with zinc as the myosin cofactor. Zinc possesses five stable isotopes, 64Zn, 66Zn, 67Zn, 68Zn, and 70Zn, whose relative abundances are 48.6%, 27.9%, 4.1%, 18.8%, and 0.6%, respectively, wherein 67Zn is magnetic (I = 5/2) while the other four isotopes are nonmagnetic (I = 0). The standard reaction media were used but containing the zinc chlorides instead of the magnesium chlorides, viz. 5 mM 67ZnCl2, 64ZnCl2, or 68ZnCl2. Two independent series of experiments were performed for enzyme preparations isolated from two different animals, and the experiments with each zinc isotope were repeated at least three times. It is known that Zn2+, as a cofactor of myosin, is less efficient than Mg2+. Indeed, the enzyme activity in the presence of the ions of the nonmagnetic zinc isotopes was lower than in the presence of magnesium ions. However, the rate of ATP hydrolysis in the presence of the magnetic isotope (67Zn) was 50–70% higher than that found for the nonmagnetic zinc isotopes. Thus, similarly to the experiments with magnesium, the acceleration of the enzymatic hydrolysis of ATP was found in the experiments with zinc. The myosin-catalyzed hydrolysis of ATP is accelerated by the nuclear spin of the magnetic isotope—the nuclear spin catalysis. At this, it is important to highlight that the rate of the spontaneous ATP hydrolysis in the experiments with the different magnesium or zinc isotopes, magnetic or nonmagnetic ones, in the same reaction media containing all the components, except for the enzyme, was the same. The catalytic MIE are observed only at the enzymatic hydrolysis of ATP (Koltover et al. 2014, 2016, 2018, 2020).

A small but statistically reliable catalytic effect of the nuclear spin of 25Mg was found in the ATP hydrolysis driven by the Mg-dependent ATPase of the myometrium plasma membranes (Koltover et al. 2020). Meanwhile, no MIE has been detected in the ATP-dependent reaction catalyzed by firefly luciferase (Smirnova et al. 2018). This enzyme catalyzes the reaction of oxidation of luciferin by molecular oxygen in the presence of the Mg-ATP complex. At the first step, luciferase hydrolyzes ATP, not to ADP and phosphate (Pl) as done by myosin or mitochondrial H+-ATPase, but to ADP and pyrophosphate (PPl). At this, due to the energy of the ATP hydrolysis, adenylation of luciferin occurs to give luciferyl adenylate. In the second step, luciferyl adenylate is oxidized by atmospheric oxygen being converted into the final reaction product, oxyluciferin. Oxyluciferin is formed in the electronically excited state and its transition to the ground state is accompanied by the emission of light in the visible region of the spectrum. In the experiments with different isotopes of magnesium, no MIE have been found. The kinetics of the ATP-dependent oxidation of luciferin catalyzed by luciferase does not depend on the type of magnesium isotope (Smirnova et al. 2018).

There are reports about MIE in the experiments with creatine phosphate kinase and phosphoglycerate kinase. It was reported that the yield of ATP in the reactions driven by these enzymes was twice as high with 25Mg than that in the reactions with nonmagnetic 24Mg or 26Mg. Besides, the beneficial MIE of calcium (43Ca versus 40Ca) and zinc (67Zn versus 64Zn) were detected with these enzymes (see refs. in Buchachenko et al. 2020). The same research team reported about the magnetic isotope effects of Mg and Zn in their experiments with isolated DNA polymerase (Buchachenko et al. 2013). However, in similar experiments with creatine phosphokinase, British scientists have failed to detect MIE (Crotty et al. 2012). Actually, in the strict sense, creatine phosphokinase is not an enzyme for the synthesis or hydrolysis of ATP. This enzyme (also defined as creatine kinase) catalyzes either the transfer of high-energy phosphate group (~Pi) from the creatine phosphate molecule to ADP to produce ATP or the reverse reaction of transfer of ~Pi from ADP to creatine to form creatine phosphate as the “energy depot” of muscle fiber. In this case, the high-energy phosphate bond is neither broken nor formed de novo (see Nelson and Cox 2008).

Thus, MIE have been detected in the enzymatic reactions of hydrolysis of ATP, in which the released energy of the ATP hydrolysis is converted totally, as in the case of muscle myosin, or partially, as in the case of mitochondrial H+-ATPase, into the mechanical energy. Namely, the acceleration of the chemo-mechanical cycle of the enzyme via the nuclear spin of the magnetic isotope, the nuclear spin catalysis, has been detected.

As a kinetical phenomenon, MIE is due to the universal law of conservation of the angular momentum, in this case—the electron spin. It unambiguously indicates that there is a rate-limiting step, i.e., a spin ban in the process under study (Buchachenko et al. 1978; Zeldovich et al. 1988). Therefore, factual evidence of MIE, on its own, indicates that there is a rate-limiting step in the enzymatic ATP hydrolysis driven by the biomolecular motor, and this “bottle-neck” is accelerated by the nuclear spin of 25Mg or 67Zn. The possible mechanisms of the discovered MIE are discussed in (Koltover 2017, 2021). The explanation of the nuclear spin catalytic effects in the ATP hydrolysis reactions, driven by the biomolecular motors, seems to be as follows. It was experimentally proved, long ago, that the ATP hydrolysis triggers the electron-conformational interactions in the active center of the enzyme, thereby producing the conformational changes in the enzyme macromolecule. In essence, there is a deformation excitation of the macromolecule owing to the energy released from the ATP hydrolysis (Volkenstein 1983). Meanwhile, the energy released from the ATP hydrolysis is not high enough to trigger the electron-conformational excitation into the singlet excited state. This energy is sufficient for a transition to the lower triplet state, but such a transition from the ground singlet state (S = 0) to the triplet state (S = 1) is prohibited by the spin conservation law. The magnetic field of the isotope’s nuclear spin, 25Mg or 67Zn, removes the spin ban and thereby provides the necessary spin conversion of the electronic-conformational state of the macromolecule into the triplet state. Thus, the chemo-mechanical cycle of the enzyme is accelerated. A similar mechanism has been proposed to explain the effects of the external magnetic fields on dislocation mobility and mechanical strength in solid-state physics (Kveder et al. 1982).

Future outlooks

The beneficial effect of 25Mg that was discovered in the experiments with yeast cells, i.e., acceleration of the post-radiation recovery of the cells enriched with 25Mg, demonstrates, in principal, a possibility to create new effective radioprotectors based on the magnetic isotopes. In nature, however, cells and tissues contain mostly nonmagnetic isotopes. The content of magnetic 25Mg is 10.13% while the content of the magnetic 67Zn is only 4.1%. Correspondingly, there is a problem with ensuring the delivery of the magnetic isotopes “in the right place at the right time.”

There are reports about the difference in biomedical effects of different isotopes of xenon (Li et al. 2018). In modern medicine, this gas is used as a means for general inhalation anesthesia, “xenon anesthesia,” at the treatment of mental and somatic disorders. In the cited work, the xenon anesthetic potency of different isotopes of xenon was studied in experiments with laboratory mice. Two magnetic isotopes, 131Xe (nuclear spin I = 3/2) and 129Xe (I = ½), and nonmagnetic isotopes 132Xe (I = 0) and 134Xe (I = 0) were used in the separate groups of the animals. It was found that the anesthetic potency of the magnetic isotopes is essentially lower in comparison with the nonmagnetic isotopes. The authors believe that the xenon magnetic isotopes exert their effects by influencing the reactions of the reactive oxygen species involving the anion-radical of oxygen, О2•- (Li et al. 2018). In our opinion, there may be another, more probable, explanation of the xenon magnetic isotope effects. As it is known, xenon anesthesia initiates the physiological processes which depend on the efficiency of the relevant enzymatic reactions. Xenon is a gas, the molecules of which are intercalated into the intracellular and intercellular aqueous solutions. It is also known that enzymatic reactions are accompanied by conformational changes in the enzyme macromolecules. During the conformational change, the positions of the atomic groups of the macromolecule are changed. At this, there occur processes of dehydration and rehydration of electrically charged amino groups of the proteins. Meanwhile, there are two different isomers of water molecules differing in mutual orientation of hydrogen nuclear spins, namely: ortho-H2O, with a parallel orientation of the hydrogen nuclear spins, and para-H2O with an antiparallel orientation of the hydrogen nuclear spins. At this, the ortho-H2O molecules, compared to para-H2O molecules, have a predominant affinity to L-amino acids of proteins (Scolnik et al. 2006). The spin-rotational interactions of protons in water molecules are too weak to ensure the proper efficiency of necessary ortho/para transitions, while the magnetic fields of 131Xe and 129Xe occur strong enough to provide the conversion of the water isomers, and, thereby, adversely altering efficiency of the relevant enzymatic reactions, reduce the anesthetic potency of the xenon inhalation.

It is also of interest that the essentially different biomedical effects were revealed in the experiments with different isotopes of lithium (see refs. in Lakota and Greguš 2022). It is well known that ions of lithium (Li+) are toxic. In low doses, however, this element, similarly to mercury and other toxic chemicals, produces favorable hormesis effects, i.e., enhancement of adaptive responses of organisms. Lithium salts have long been used in medicine, in part, in psychiatry as the remedy against some neurodepressive diseases. Meanwhile, there are two stable isotopes of lithium, namely, 7Li (natural abundance about 93%, nuclear spin I = 3/2) and 6Li (abundance about 7%, nuclear spin I = 1), so that both isotopes are magnetic (Grant, Harris1996). About 40 years ago, there were studied effects of lithium salts, added to drinking water, on the behavior of female rats, i.e., their behavior characteristics prior to gestation, during gestation, and during the lactation period (Sechzer et al. 1986). By comparison with the control animals, the rats, which were exposed to 7Li or natural Li (natural isotope composition), have demonstrated worse maternal behavior. Namely, by comparison with the control animals, these animals demonstrated worse nest building, worse nursing, worse grooming of pups, worse reacting for food, and worse state of alertness. Meanwhile, the same behavior characteristics of the rats, exposed to 6Li, were much better, even excessive, by comparison with the control animals. In essence, the behavior characteristics of the rats, which were drinking water with 6Li, were opposite to those which were drinking water with 7Li or natural Li (Sechzer et al. 1986). Considering this curious difference in the psychiatric effects of different magnetic isotopes of lithium, one should take into account that, similarly to molecules of xenon, ions of lithium intercalate into intracellular and intercellular water of tissues and cells. In this respect, it would be of interest to quantitatively investigate and compare the effects of 6Li and 7Li on the ratio of the water isomers, ortho-H2O and para-H2O. It is possible that the nuclear spin of 6Li, which is one and a half times less than the nuclear spin of 7Li, creates the magnetic field that provides the ratio of the water isomers, which is most favorable for providing the necessary biochemical reactions and related physiological processes. However, it should also be taken into account that the differences in the effects of the isotopes might arise from differences in contents of contaminant chemical elements, impurities, in the used preparations of the isotopes. The relevant analytical work, in order to test and determine the chemical impurities in isotope preparations, is always necessary in experiments of his kind.

The magnetic isotope effect of 25Mg, which was discovered in our experiments with myosin, seems to be tightly related to the problems of the impact of electromagnetic fields on living organisms. The biological effects of weak electromagnetic fields of variable frequencies are known for a long time but are still poorly understood (Binhi et al. 2006; Romeo et al. 2022; Krylov and Osipova 2023). Furthermore, the geocosmic oscillations, caused by the movement of the Earth in heterogeneous and anisotropic space-time, have long been known. In the magnetic field of Earth, the strength of which is about 0.05 mT, the nuclear magnetic resonance frequencies for the magnetic nuclei fall within the range between approximately 50 and 2000 Hz. In this respect, it is worthy to note the anomalous scattering of the results of measuring the actomyosin enzyme activity in the works of Simon Shnoll (2013) about 60 years ago. Trying to understand the causes of the unexpectedly large scatter in the results of the measurements of the ATPase activity of the actomyosin preparations, it was assumed in the cited work that this phenomenon is due to some special properties of actomyosin, namely, due to “diurnal conformational fluctuations” or “macroscopic fluctuations” caused by geocosmic variations (Shnoll 2013). Inasmuch as the nuclear spin moment of the magnetic isotope, 25Mg, is prone to external magnetic fields, it may be the direct relationship to this problem. Basing on the beneficial MIE, which were discovered in our experiments with myosin, on the nuclear spin catalysis background, one can suggest that the macroscopic fluctuations of the enzymatic activity in the experiments with actomyosin, which were cited in (Shnoll 2013), stem from the variations in geocosmic electromagnetic fields and, thereby, from the changes in the interactions of the geocosmic magnetic fields with the nuclear spin of the magnesium magnetic isotope, 25Mg, in the active center of the actomyosin. Although the natural abundance of the magnetic 25Mg is only about 10%, it may serve as the primary magnetoreceptor in the actomyosin and other biomolecular motors in living nature. In the biomolecular motors, which operate on the nonmagnetic isotopes of magnesium, the similar magnetoreceptor effects can be performed by the nuclear spins of hydrogen (1H, I = 1/2) and phosphorus (31P, I = ½). However, the catalytic activity of 25Mg is essentially higher, since the nuclear spin of 25Mg (I = 5/2) is 5 times greater than the nuclear spins of 1H and 31P. Accordingly, 25Mg, the hyperfine interaction constant ≈21 mT, creates an essentially stronger local magnetic field in the active center of the biomolecular motor, thereby making it more vulnerable to geomagnetic variations. Inasmuch as the electron and nuclear spin moments can be changed by external magnetic fields, this creates the fundamental possibility of exercising the control over efficiency and reliability of biomolecular nanoreactors with the help of electromagnetic fields.

Thus, the recent developments in this new field of biophysics, the nuclear spin catalysis, highlight promising venues for future research of the nuclear spin catalysts in biophysics with possible applications of the magnetic isotopes in biomedical physics, including radiation medicine and biomedical effects of electromagnetic fields.

Acknowledgements

The isotope and elemental compositions of all the samples studied in our experiments were controlled by the methods of high-resolution mass spectrometry and atomic emission spectrometry in the Analytical Center of Institute of Microelectronics Technology Problems and High Purity Materials of RAS, Chernogolovka. My heartfelt appreciation to Dr. Vasiliy K. Karandashev, head of the Analytical Center, and his coworkers for so fruitful cooperation.

Funding

The work was supported by the Ministry of Science and Higher Education of the Russian Federation (theme AAAA-А19-119092390041-5). No grants or other support were received during the preparation of this manuscript.

Data availability

No new data were created in this study.

Declarations

Ethics approval

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Consent for publication

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Conflict of interest

The author declares no competing interests.

Footnotes

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Change history

11/8/2023

Changes have been made in the reference citations found in page 2 and page 3.

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