Article pubs.acs.org/accounts
New Possibilities for Magnetic Control of Chemical and Biochemical Reactions Anatoly Buchachenko*,†,‡,∥,⊥ and Ronald G. Lawler*,§ †
Institute of Chemical Physics, Russian Academy of Sciences, 4 Kosygin Street, 119991 Moscow, Russian Federation Institute of Problems of Chemical Physics, Russian Academy of Sciences, 142432 Chernogolovka, Russian Federation ∥ Scientific Center in Chernogolovka, 142432 Chernogolovka, Russian Federation ⊥ Yaroslavl State University, 150003 Yaroslavl, Russian Federation § Department of Chemistry, Brown University, Box H, 324 Brook Street, Providence, Rhode Island 02912, United States ‡
CONSPECTUS: Chemistry is controlled by Coulomb energy; magnetic energy is lower by many orders of magnitude and may be confidently ignored in the energy balance of chemical reactions. The situation becomes less clear, however, when reaction rates are considered. In this case, magnetic perturbations of nearly degenerate energy surface crossings may produce observable, and sometimes even dramatic, effects on reactions rates, product yields, and spectroscopic transitions. A case in point that has been studied for nearly five decades is electron spin-selective chemistry via the intermediacy of radical pairs. Magnetic fields, external (permanent or oscillating) and the internal magnetic fields of magnetic nuclei, have been shown to overcome electron spin selection rules for pairs of reactive paramagnetic intermediates, catalyzing or inhibiting chemical reaction pathways. The accelerating effects of magnetic stimulation may therefore be considered to be magnetic catalysis. This type of catalysis is most commonly observed for reactions of a relatively long-lived radical pair containing two weakly interacting electron spins formed by dissociation of molecules or by electron transfer. The pair may exist in singlet (total electron spin is zero) or triplet (total spin is unity) spin states. In virtually all cases, only the singlet state yields stable reaction products. Magnetic interactions with nuclear spins or applied fields may therefore affect the reactivity of radical pairs by changing the angular momentum of the pairs. Magnetic catalysis, first detected via its effect on spin state populations in nuclear and electron spin resonance, has been shown to function in a great variety of well-characterized reactions of organic free radicals. Considerably less well studied are examples suggesting that the basic mechanism may also explain magnetic effects that stimulate ATP synthesis, eliminating ATP deficiency in cardiac diseases, control cell proliferation, killing cancer cells, and control transcranial magnetic stimulation against cognitive deceases. Magnetic control has also been observed for some processes of importance in materials science and earth and environmental science and may play a role in animal navigation. In this Account, the radical pair mechanism is applied as a consistent explanation for several intriguing new magnetic phenomena. Specific examples include acceleration of solid state reactions of silicon by the magnetic isotope 29Si, enrichment of 17O during thermal decomposition of metal carbonates and magnetic effects on crystal plasticity. In each of these cases, the results are consistent with an initial one-electron transfer to generate a radical pair. Similar processes can account for mass-independent fractionation of isotopes of mercury, sulfur, germanium, tin, iron, and uranium in both naturally occurring samples and laboratory experiments. In the area of biochemistry, catalysis by magnetic isotopes has now been reported in several reactions of DNA and high energy phosphate. Possible medical applications of these observations are pointed out.
1. INTRODUCTION
a problem solved by Wigner in 1933 to describe magnetic catalysis of the interconversion of ortho and para hydrogen.6 The radical pair mechanism (RPM) was later refined7 by inclusion of increasingly realistic representations of the interactions of electron spins, the dynamics of the quantum process, and the time and space relations between the reacting partners. During the ensuing decades the unifying influence of the RPM has given rise to a variety of experimental and theoretical applications of CIDNP and CIDEP to the chemistry and physics of free radicals.8
1.1. Some History
It has been a half-century since the appearance of the first reports of unusual intensities of electron spin resonance1 and nuclear magnetic resonance2,3 spectra during rapid chemical reactions. These effects, termed chemically induced electron (nuclear) polarization, CIDE(N)P, were observed during reactions known to produce free radicals. The effects were in due course shown4,5 to arise from electron- and nuclear-spin effects on the recombination probability of pairs of free radicals formed in reactions occurring during high-energy processes in liquids induced by thermolysis, photolysis, radiolysis, or a handful of exothermic redox reactions. The quantum mechanical model employed was in essence a rediscovery of © 2017 American Chemical Society
Received: December 13, 2016 Published: February 20, 2017 877
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dependent effects, and in almost all examples anomalous spin polarization was detected by magnetic resonance.
In 1971, one of the present authors pointed out that the magnetic effects implied by the RPM should also be observable as a dependence of the yields of chemical reactions on an externally applied field and also on the presence or absence of isotopes with nuclear spins.9,10 The latter effect was expected to be readily distinguishable from, and perhaps larger in magnitude than, the more familiar mass-dependent isotope effect. In 1970, the observation of unprecedentedly large 13C nuclear polarizations in radical products11 inspired a targetoriented search for the predicted 13C nuclear spin effect on the corresponding reaction rates. Its discovery was announced by the other author in 1976;12 the new effect was christened magnetic isotope effect (MIE).12 Similar effects have now been detected in numerous studies and summarized in reviews and books.13−15
1.3. Why This Account?
As the field of magnetic polarization matured and examples of plausible MIEs and related magnetic field effects in organic free radical reactions multiplied, examples began to appear of less well-documented magnetic effects that might be explainable by the RPM.16 The purpose of the present Account is to summarize and explain the main ideas of proposed magnetic control via the RPM in several of these unfamiliar and less well characterized examples from chemistry and biochemistry, related to biology, medicine, ecological and earth science, and materials science. The emphasis will be on examples of MIEs. Effects of external fields will be mentioned only as they supplement the interpretation of the MIE experiments or suggest processes where an MIE might be expected. This will exclude many examples of magnetic field effects on enzymecatalyzed reactions, which are summarized in several reviews.17−19 We also note, but will not discuss, the fascinating possibility that magnetic effects on animal navigation may have a component involving radical pairs.20 Most of these examples lie well outside the realm of the now well-documented liquid phase reactions of free radicals. Furthermore, efforts to test the reproducibility of some of the experimental results are still in the early stages and not free from controversy.10,21−23 Nevertheless, it would appear propitious, on the eve of the 50th anniversary of CIDNP, to call attention to these phenomena in the hope that they will receive the closer scrutiny that they, in our opinion, deserve.
1.2. The Radical Pair Mechanism
The best examples of the success of the RPM are chemical processes where the continuum of energy levels represented by the reactants and products passes through intermediate states in which, for a time, a sparse set of magnetically active states become uncoupled from the other states of the reacting atoms. The resulting spin chemistry arises from a delicate interplay, shown in the scheme below, among the following parameters and conditions: (1) magnetic perturbations, kST, including the hyperfine and dipolar interactions between the electron and nuclear spins, differential Zeeman interactions, or resonant magnetic fields that mix states of different multiplicities; and a zero-order splitting, ΔEST, of the singlet state (S) and three triplet states (T−, T0, T+) by Zeeman, exchange, or other interactions, which is not much larger than kST; (2) competing mixing processes, k′, such as spin−orbit interactions or spin relaxation that can also lead to S−T mixing but reduce the catalytic effect; (3) radical pair lifetime, τ, long enough to allow magnetic catalysis but sufficiently short to prevent complete mixing by competing processes; (4) an alternative, spin-independent chemical route that scavenges radicals, kscav, forming products R−X and preventing formation of the recombination product, R− R′. These processes are shown in Figure 1. Unless the mix of rates and energies is just right, the magnetic perturbations cannot compete with alterative pathways and no effect on the reaction path is observed. Examples of processes where the quantum and kinetic conditions produce observable effects have been extensively reproduced and reviewed.8,13−15 In most cases, evidence for the required intermediates existed before the observation of spin
2. SOLID-STATE REACTIONS These reactions deserve special attention because of their potential importance for materials science, mineralogy, geochemistry, electronic materials, and solid state mechanics. 2.1. Oxidation of Silicon
The oxidation of silicon crystals has been found to be strongly accelerated by an external magnetic field and by the internal field of the magnetic nucleus 29Si.24 Atoms of 29Si are oxidized by molecular oxygen twice as fast as atoms of 28Si and 30Si, the spinless, nonmagnetic nuclei (Figure 2). Both effects support a mechanism for solid-state silicon oxidation that is electron and nuclear spin selective, involving pairs of paramagnetic intermediates. One such mechanism is the following. Insertion of triplet O2 into the Si−Si bond produces a triplet-born radical pair that can
Figure 1. Reaction scheme for singlet-born radical pair (see text for explanation of symbols). Fast S−T mixing increases the yield of R−X and decreases R−R′. The relative yields are the opposite for a tripletborn pair.
Figure 2. Yield, Δ, of silicon oxidation products (in arbitrary units) as a function of time for 28Si (●) and 30Si (■) (1) and for 29Si (2). 878
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reducing the plasticity of host crystals such as NaCl. The stopping power of the trap would be lowered, however, by reduction to Ca+ by electron transfer from Cl− (k1). Back electron transfer (k−1) would then be inhibited by magnetic catalysis of S−T mixing (km) in the presence of a magnetic field (H), prolonging the lifetime (1/k) of Ca+ and increasing plasticity. This mechanism predicts the observed softening of ionic crystals and strengthening of covalent crystals in a magnetic field27 and, importantly, that it occurs in diamagnetic solids and needs no presence of paramagnetic impurities.28 The decisive test for the validity of a RPM for plasticity would be experimental observation of the radical pair [dislocation + stopper]. Although direct observation of the radicals, for example, by electron paramagnetic resonance or optical spectroscopy seems lacking, the phenomenon of microwave induced plasticity provides some evidence to support the intermediacy of the pair.28 In this case, the requisite S−T mixing is induced by connecting all three nonreactive triplet levels to the singlet state as shown in Figure 3. It shows the Zeeman levels of singlet (S) and triplet (T)
form products only via the singlet state. The MIE arises from selective T−S conversion by the magnetic isotope 29Si. SiSi + 3O2 ↔ [28,30Si• •O2 Si]T → [28,30Si• •O2 Si]S
28,30
→ products
SiSi + 3O2 ↔ [29Si• •O2 Si]T → [29Si• •O2 Si]S
29
→ products
The observation that 28Si and 30Si have the same oxidation rates seems to rule out a mass isotope effect10 (Figure 2). 2.2. Decomposition of Inorganic Carbonates
Miller et al.25 have reported a mass-independent isotope effect on the thermally induced decomposition of metal carbonates: The volatile CO2 product appears to be enriched in 17O, while the residual solid metal oxide product is 17O depleted to about the same extent. Furthermore, the 16O and 18O content of the products is unchanged. These results are consistent with a key step involving intramolecular one-electron transfer, which generates a radical pair in the singlet spin state: (M2 + CO32 −)S ↔ (M+ CO3−)S
where M is Ca or Mg. Back electron transfer via the S state, with no net reaction, is inhibited by catalytic S−T mixing by the magnetic isotope 17O. −
−
(M+ 17OCO2 )S → (M+ 17OCO2 )T → (M+ 17OCO O−)T → 17OCO + (M+ O−)T
These results suggest that the possibility of magnetically induced fractionation of oxygen isotopes needs to be considered in studies related to geochemistry, climatology,and other areas of the Earth sciences.
Figure 3. Scheme of the energy levels in zero (H = 0) and in high (H ≫ 0) magnetic fields.
states of the radical pair in zero and in high magnetic fields. In the former case the singlet and the three triplet states are degenerate, but in high magnetic fields the triplet levels are split by the Zeeman interaction, and microwave transitions must be employed to promote the mixing of all three levels. Experimental observations of microwave effects on crystal dislocations are in agreement with the predictions. It has also been proposed29 that this mechanism of transformation of dangerous elastic energy into the safer energy of plastic flow by microwave stimulation of the mobility of dislocations might be employed as a way of controlling earthquake sites and reducing catastrophic energy release. The RPM also predicts nuclear spin induced magnetic catalysis of the dislocation mobility by the ion stoppers such as Ca2+, Mg2+, and Zn2+, which have magnetic isotopes (43Ca, 25Mg, 67Zn).30
2.3. Magnetic Chemistry of Crystal Plasticity
There is some evidence that the mechanism of crystal plasticity may involve a component based on solid state electron transfer reactions,which are magnetically controlled.26 Magnetoplasticity, the influence of magnetic fields (both permanent and oscillating) on the hardness and plasticity of diamagnetic crystals, including NaCl, PbS, LiF, and Si, seems to be enigmatic, since the energy of interaction between diamagnetic ions or atoms and a magnetic field should certainly be negligible. A proposed mechanism explaining magnetoplasticity27 is shown in Scheme 1 for the particular case of doubly charged ions such as Ca2+present as “stoppers” that form a “Coulomb trap”, which reduces the mobility of dislocations, thereby
3. CHEMISTRY OF ISOTOPE FRACTIONATION As mentioned in the Introduction, the first example of magnetic isotope fractionation was discovered as 13C enrichment via photocleavage of ketones.12 Another reaction, with obvious potential practical applications, is uranium isotope fractionation that has been reported to occur similarly in the photolysis of uranyl salts in the presence of the substituted phenols, PhOH.31 The photoinduced reaction generates a triplet radical pair [UO2H• •OPh]T, which undergoes fast triplet−singlet conversion if it contains magnetic 235U nuclei (Scheme 2); then spin allowed reverse hydrogen atom transfer in the singlet pair regenerates phenol and UO22+ uranyl ion enriched with magnetic 235U nuclei. Triplet−singlet conversion of the pairs
Scheme 1. Chemical Evolution of the Dislocation in Magnetic Field
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singlet-born, enzyme-bound radical pair [ROPO 3 −• M + R′PO32−] formed from the phosphorus acceptor, ROPO32−, the metal cation, M2+, and a proximal phosphate donor, R′PO32− (Figure 4). The requisite one-electron transfer is
Scheme 2. 235U Magnetic Isotope Catalysis of Back-Reaction of Radical Pair, Formed by Photoreduction of Uranyl Ion by Phenol
with nonmagnetic 238U nuclei delays and gives a chance for the radicals to escape, carrying 238U nuclei into the ultimate reaction product, UF4 (reactions not shown). The starting uranyl salt therefore accumulates the magnetic nuclei 235U. Magnetically induced fractionation of magnetic and nonmagnetic isotopes has also been reported for several other isotopes: oxygen,32 silicon,33 sulfur,34 germanium,35 tin,36 and mercury.37 Since the degree of separation depends on the magnitude of the electron−nuclear coupling, which often increases with atomic number, in heavier isotopes it may exceed the mass-dependent fractionation by 1 or even 2 orders of magnitude.38
4. ECOLOGY AND BIOGEOCHEMISTRY An ecologically important example of mass-independent isotope fractionation involves the use of mercury isotopes as reporters of the chemical, biochemical, and geological history of naturally occurring samples. Several reports have appeared39 in which the abundance in natural samples of Hg isotopes with nuclear spin (odd isotopes) deviates markedly from those without spin (even-isotopes). The nonspin isotopes, however, do exhibit a mass-dependent isotope effect. This is consistent with a contribution to the natural processes from both RPM and nonradical mechanisms.39 Another ecologically significant observation is magnetically induced isotope fractionation in the photo-oxidation of water by molecular oxygen that is thought to be a means of elucidating global processes of oxygen production and consumption in Nature.40 Photo-oxidation was shown to transfer 17O to water slightly faster than 18O, the difference increasing in a high magnetic field. This has been interpreted to indicate that a significant part of the oxygen exchange process occurs via the disproportionation reaction between two independently formed HO2 radicals. The presence of the magnetic isotope increases the population of singlet, reactive, pairs by S−T conversion of a portion of the 3/4 of random encounters that produce the nonreactive triplet. An unexpectedly large 33S enrichment relative to 34S and 36S in high temperature reduction of sulfate by amino acids has been explained by the intermediacy of thiol cation radical/ disulfide anion radical pairs.41It was also proposed that these results may indicate that a RPM effect contributes to Archean sulfur isotope anomalies observed in geochemistry. Very recently,42 a MIE for 57Fe has been observed in the biosignature of magnetotactic bacteria. It is proposed that the effect may be associated with spin transitions during Fe(III) reduction by cytochromes or other redox enzymes for which magnetic field effects have been reported.17−19
Figure 4. Proposed mechanism of phosphorylation.
25
Mg2+ catalyzed MIE for
thought to be driven by changes in the state of hydration of the bound metal ion.43 The phosphorylating step is then assumed to take place by addition of the ROPO3−• radical to the phosphate donor (2), followed by ejection of a radical R′, for example, HO• (3), which is then reduced by the monovalent metal ion bound in the same enzyme site. The increase in catalysis reported for magnetic metal ion isotopes (e.g., 25Mg) is assumed to arise from inhibition of reverse electron transfer in step 1 via the radical pair singlet state by inducing S−T conversion to the triplet state that is still capable of undergoing the next reaction step. This mechanism seems to require the presence of at least two metal ions at the active site. It is therefore “turned on” at higher ion concentrations than are normally required for the conventional nonradical, nucleophilic mechanism of phosphorylation with which it may compete both positively and negatively. The RPM also seems to be “turned off” by paramagnetic ions, most notably Fe2+. The latter effect has been used to explain the failure of some attempts to reproduce the MIE and magnetic field effects.21−23,44,45 Representative reports of magnetic catalysis of enzymatic ATP synthesis and DNA replication are described below, and possible mechanisms based on the RPM are discussed and justified. 5.1. Magnetic Effects in Enzyme Catalyzed ATP Synthesis
The first report of a magnetic isotope effect operating in a biochemical system was the fractionation of the magnetic isotopes 199Hg and 201Hg by creatine kinase (CK).46 A related example, illustrated in Figure 5, shows the enzymatic activity of CK loaded with the isotopically pure ions 24Mg2+, 25Mg2+, and 26 Mg2+. Kinases with nonmagnetic isotopic nuclei 24Mg and 26 Mg display identical activity, while the kinase with magnetic nucleus 25Mg is almost two times more active.47
5. CHEMISTRY OF ENZYMATIC REACTIONS The radical pair mechanism has been proposed to operate in some aspects of enzymatic phosphorylation. In particular, catalytic enhancement by the magnetic isotopes of Mg2+, Ca2+, and Zn2+ has been detected in enzymatic phosphorylation reactions involved in the biosynthesis of ATP and DNA. In all cases it has been proposed that the critical step (1) involves a 880
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reports.14,22,44,55 They may, however, explain some aspects of the reported failure to reproduce the MIE.21,45 5.2. Magnetic Control of DNA Synthesis
DNA synthesis is known to occur via polymerases, which attach a nucleotide phosphate monomer molecule to the growing DNA chain. The chemical mechanism of the attachment is traditionally thought to be exclusively nucleophilic, with no evidence of spin-carrying, paramagnetic intermediates.56 However, under some conditions the activity of β-polymerase has been found to depend on the nuclear magnetic moments of the ions 25Mg2+, 67Zn2+, and 43Ca2+, which, unlike the effect with ATP synthesis, strongly suppress polymerase activity (Figures 7 and 8). A proposed explanation of the reversal of the MIE involves the intermediacy of an addition product of a ribose oxy radical on the DNA strand to the incoming nucleotide triphosphate.57−59 The radical addition product is capable of undergoing side reactions that prevent elongation of the DNA, decreasing the yield of DNA from the nonradical route. It is also found, remarkably, that the ubiquitous polymerase chain reaction (PCR) is suppressed by 25Mg in a manner similar to that found for polymerase β.60 The RPM origin of this effect is supported by the observation of an increase in the rate of DNA synthesis in a high magnetic field in the presence of enriched 25Mg2+. It is proposed that this effect arises from a reduction in the MIE by removing the T− and T+ states from the S−T mixing process that inhibits DNA synthesis. Samples with increased amounts of the nonmagnetic Mg isotopes exhibit a weak decrease in rate in a high field under the same reaction conditions, presumably because the g-factor difference of the radical pair induces S−T mixing as the field is increased. As in the case of ATP synthesis, the magnetic effects are strongly suppressed by added Fe2+.
Figure 5. Rate of ATP synthesis by CK as a function of magnesium isotopes. The rate A is given as the radioactivity of 32P-ATP measured as a number of scintillations/min/mg of total amounts of protein (pure CK); concentration of MgCl2 is 15 mM.
Similar effects were detected48,49 for CK loaded with isotopic pairs 64Zn2+/67Zn2+ and 40Ca2+/43Ca2+, as well as in enzymatic activity of isolated mitochondria,50 phosphoglycerate kinase,51 and pyruvate kinase.52 A catalyzing function of mitochondrial phosphorylation in a higher organism has been reported in rats.47,53 The in vivo effect is shown in Figure 6. Such a stimulation of ATP synthesis in
5.3. Possible Medical Applications
As was mentioned above, the ability of relatively high concentrations of magnetic isotopes of catalytically active divalent metal ions to increase the rate of ATP syntheses may prove clinically significant as a way of stimulating the energetics of critical tissues. Analogous possibilities come to mind for applications of the ability of the same isotopes to inhibit DNA synthesis, perhaps as a novel type of tumor growth inhibitor. To this end, the magnetic isotopes 25Mg2+, 67Zn2+, and 43Ca2+ were tested as a means to kill cancer cells,14,22,59 and exceptionally high sensitivity of cell-killing to magnetic isotopes was observed. Careful comparison of the effects of magnetic and nonmagnetic isotopes and applied fields will be required to establish the extent to which a possible MIE competes with differences in susceptibility of normal and cancer cells to the mode of metal ion delivery; but the initial results are promising. Other medical applications of the MIE that have been suggested include transcranial magnetic stimulation, which is used to treat and study cognitive disorders and neurological diseases.
Figure 6. Recovery degree (RD) of ATP production in rat heart muscle as a function of amount of the magnesium ions delivered by intramuscular injection. RD stands for the extent of restoration of a hypoxia-suppressed myocardium tissue ATP content, that is, zero RD means total ATP depletion, while RD = 1.0 shows a complete restoration of normal prehypoxia myocardium ATP level.
heart muscle might be used to prevent hypoxia and other pathologies related to the deficiency of ATP. The use of the nonradioactive isotope 25Mg would prove to be an advantage in exploring possible clinical applications of this effect in humans. The RPM is also supported by the report54 that ATP synthesis by creatine kinase, under conditions similar to those exhibiting a MIE, varies with an externally applied magnetic field of the same order of magnitude as the hyperfine couplings expected for 31P and 25Mg in the proposed paramagnetic intermediates, as predicted by the RPM.10 Finally, it is worth noting that the possible effects of impurities on the metal ion MIE associated with phosphorylation have been explored and found to be insignificant for the materials used in the above
6. CONCLUSIONS Magnetic control of the reactivity of paramagnetic intermediates is a concept that may in principle be extended to many phenomena. These include solid state chemistry, chemistry of crystal plasticity, selective fractionation of magnetic isotopes, and medicinal chemistry. It may manifest itself in isolated mitochondria and in intact living organisms, stimulating ATP synthesis and potentially being used to treat ATP deficiency in 881
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Figure 7. Rate of DNA synthesis by polymerase β as a function of magnesium and zinc ion concentration in pairs 25 Mg2+/26Mg2+ (B), and 64Zn2+/67Zn2+ (C).
24
Mg2+/25Mg2+ (A),
radical mechanisms, which may have very useful applications and important consequences for the understanding of isotope effects. Documentation of some of the suggested mechanisms and experimental results is still in the very early stages. Nevertheless, it is hoped that consolidation of the diverse observations and explanations presented here will stimulate further research to probe these extensions of the radical pair mechanism.
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AUTHOR INFORMATION
Corresponding Authors
*A.B. Phone: +7-495-9397128. Fax: +7-495-9382484. E-mail:
[email protected]. *R.L. Phone: 1-603-284-6321. E-mail: ronald_lawler@brown. edu.
Figure 8. Rate of DNA synthesis by β polymerase isolated from HL-60 as a function of concentration of 40Ca2+ and 43Ca2+ ions. A is the tritium activity in counts/min/mg incorporated into DNA from labeled precursor.
ORCID
Anatoly Buchachenko: 0000-0002-4064-9328
cardiac diseases. It may affect enzymatic DNA synthesis, induce the killing of cancer cells, and explain some of the long-term effects of transcranial magnetic stimulation against cognitive deceases. The polymerase chain reaction, which has become an indispensable tool in molecular biology, appears to exhibit and may be susceptible to control by magnetic effects. Magnetic isotope effects have been reported for ecologically important processes in soils, natural waters, and nutrients and may contribute to the isotope ratio measurements that provide a means of monitoring and inferring the chemical, biological, and geological history of these processes. It has also been reported that magnetic control may be switched on or off by using magnetic isotopes or paramagnetic ions, respectively. It is worth emphasizing that the radical pair reactions proposed to account for the observations discussed here are not “turned on” by magnetic effects but are intrinsic to the processes described. Moreover, it is worth emphasizing that the radical pair reactions are induced by both sorts of ions, magnetic and nonmagnetic; the only difference is that it functions 2−3 times more efficiently with magnetic ions. As in the case of several examples from earlier work on CIDNP and related phenomena, the magnetic isotope and field effects simply reveal the presence of some previously unsuspected
Author Contributions
The contribution of both authors is equal. Notes
The authors declare no competing financial interest. Biographies Anatoly Buchachenko is Professor of the Institute of Chemical Physics and Moscow University and a member of the Russian Academy of Sciences. His interests are in ESR and NMR spectroscopy, molecular ferromagnetism, spin chemistry, and isotope effects in chemistry and biochemistry. Ronald G. Lawler is Professor Emeritus of Chemistry at Brown University. His research has involved applications of magnetic resonance to a variety of problems in chemistry and related areas, including CIDNP, radiation chemistry, radical ion structures and reactions, endofullerene chemistry, and comparative physiology studies using in vivo NMR.
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ACKNOWLEDGMENTS A.B. is grateful to the Russian National Scientific Foundation for financial support (Grant 14-23-00018). 882
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(25) Miller, M. F.; Franchi, I. A.; Thiemens, M. H.; Jackson, T. L.; Brack, A.; Kurat, G.; Pillinger, C. T. Mass-independent fractionation of oxygen isotopes during thermal decomposition of carbonates. Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 10988−10993. (26) Alshits, V. I.; Darinskaya, E. V.; Koldaeva, M. V.; Petrzhik, E. A. Electric amplification of the magneto-plastic effect in nonmagnetic crystals. J. Appl. Phys. 2009, 105, 063520. (27) Golovin, Yu.I. Magnetoplastic effects in solids. Phys. Solid State 2004, 46, 789−824. (28) Buchachenko, A. L. Magneto-plasticity of diamagnetic crystals in microwave fields. J. Exp. Theor. Phys. 2007, 105, 593−598. (29) Buchachenko, A. L. Magneto-plasticity and physics of the earthquakes. Can a catastrophe be prevented? Phys.-Usp. 2014, 57, 92−98. (30) Buchachenko, A. L. Magnetic Isotope Effect on the Plasticity of Diamagnetic Crystals. JETP Lett. 2007, 84, 500−501. (31) Buchachenko, A. L.; Khudyakov, I. V. Magnetic and spin effects in photo-reduction of uranyl salts. Acc. Chem. Res. 1991, 24, 177−183. (32) Buchachenko, A. L.; Yasina, L. L.; Belyakov, V. A. Magnetic and Classical Oxygen Isotope Effects in Chain Oxidation Processes: A Quantitative Study. J. Phys. Chem. 1995, 99, 4964−4969. (33) Step, E. N.; Tarasov, V. F.; Buchachenko, A. L. 29Si magnetic isotope effects in the photolysis of silyl ketones. Chem. Phys. Lett. 1988, 144, 523−526. (34) Step, E. N.; Tarasov, V. F.; Buchachenko, A. L. Magnetic isotope effect. Nature 1990, 345, 25. (35) Wakasa, M.; Hayashi, H.; Ohara, K.; Takada, T. Enrichment of Germanium-73 with the Magnetic Isotope Effect on the Hydrogen Abstraction Reaction of Triplet Benzophenone with Triethylgermane in SDS Micellar Solution. J. Am. Chem. Soc. 1998, 120, 3227−3230. (36) Buchachenko, A. L.; Roznyatovsky, V. A.; Ivanov, V. L.; Ustynyuk, Yu.A. Magnetic isotope effect in the photolysis of tin compounds. J. Phys. Chem. A 2006, 110, 3857−3859. (37) Buchachenko, A. L.; Ivanov, V. L.; Roznyatovskii, V. A.; Vorob'ev, A. C.; Ustynyuk, Y. A. Inversion of the Sign of the Magnetic Isotope Effect of Mercury in Photolysis of Substituted Dibenzyl Mercury. Dokl. Phys. Chem. 2008, 420, 85−87. (38) Buchachenko, A. L. Mass-independent isotope effects. J. Phys. Chem. B 2013, 117, 2231−2238. (39) Buchachenko, A. L. Mercury isotope effects in the environmental chemistry and biochemistry of mercury-containing compounds. Russ. Chem. Rev. 2009, 78, 319−328. (40) Buchachenko, A. L.; Dubinina, E. O. Photo-oxidation of Water by Molecular Oxygen: Isotope Exchange and Isotope Effects. J. Phys. Chem. A 2011, 115, 3196−3200. (41) Oduro, H.; Harms, B.; Sintim, H. O.; Kaufman, A. J.; Cody, G.; Farquhar, J. Evidence of magnetic isotope effects during thermochemical sulfate reduction. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 17635−17638. (42) Amor, M.; Busigny, V.; Louvat, P.; Gélabert, A.; Cartigny, P.; Durand-Dubief, M.; Ona-Nguema, G.; Alphandéry, E.; Chebbi, I.; Guyot, F. Mass-dependent and -independent signature of Fe isotopes in magneto-tactic bacteria. Science 2016, 352, 705−708. (43) Buchachenko, A. L.; Kuznetsov, D. A.; Breslavskaya, N. N. IonRadical Mechanism of Enzymatic ATP Synthesis: DFT Calculations and Experimental Control. J. Phys. Chem. B 2010, 114, 2287−2292. (44) Arkhangel’skii, S. E.; Karpov, Yu.A.; Glavin, G. G.; Kuznetsov, D. A.; Buchachenko, A. L. Isotope catalysis and isotope analysis. Russ. J. Phys. Chem. B 2013, 7, 8−10. (45) Crotty, D.; Silkstone, G.; Poddar, S.; Ranson, R.; Prina-Mello, A.; Wilson, M.; Coey, J. M. D. Reexamination of magnetic isotope and field effects on adenosine triphosphate production by creatine kinase. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 1437−1442. (46) Buchachenko, A. L.; Kouznetsov, D. A.; Shishkov, A. V. Spin biochemistry: mercury magnetic isotope effect inthereaction of creatinekinase. J. Phys. Chem. A 2004, 108, 707−710. (47) Buchachenko, A. L.; Kouznetsov, D. A.; Arkhangelsky, S. E.; Orlova, M. A.; Markarian, A. A. Spin biochemistry: magnetic
DEDICATION This Account is dedicated to the memory of Professor Nicholas J. Turro, a great scientist and friend of both authors.
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REFERENCES
(1) Fessenden, R. W.; Schuler, R. H. Electron spin resonance studies of transient alkyl radicals. J. Chem. Phys. 1963, 39, 2147−2195. (2) Bargon, J.; Fischer, H.; Johnsen, U. Kern resonanz emission linien wahrend rascher radikal reaktionen I. Aufnahmeverfahren und beispiele. Z. Naturforsch., A: Phys. Sci. 1967, A22, 1551−1560. (3) Ward, H. R.; Lawler, R. G. Nuclear magnetic resonance emission and enhanced absorption in rapid organometallic reactions. J. Am. Chem. Soc. 1967, 89, 5518−5519. (4) Closs, G. L. A Mechanism Explaining Nuclear Spin Polarizations in Radical Recombination Reactions. J. Am. Chem. Soc. 1969, 91, 4552−4554. (5) Kaptein, R.; Oosterhoff, L. J. Chemically Induced Dynamic Nuclear Polarization III. Anomalous multiplets of radical coupling and disproportionation products. Chem. Phys. Lett. 1969, 4, 214−216. (6) Wigner, E. Uber die paramagnetische Umwandlung von ParaOrtho Wasserstoff. III. Z. Phys. Chem. 1933, 23B, 28−32. (7) Freed, J. H.; Pedersen, J. B. The theory of chemically induced dynamic spin polarization. Adv. Magn. Opt. Reson. 1976, 8, 1−84. (8) Woodward, J. R. Radical pairs in solution. Prog. React. Kinet. Mech. 2002, 27, 165−207. (9) Lawler, R. G.; Evans, G. T. Some chemical consequences of magnetic interactions in radical pairs. Ind. Chim. Belges 1971, 36, 1087−1089. (10) Lawler, R. G. Criteria for establishing the existence of nuclear spin isotope effects. J. Am. Chem. Soc. 1980, 102, 430−432. (11) Lippmaa, E. T.; Pehk, T. I.; Buchachenko, A. L.; Rykov, S. V. Chemically induced dynamic nuclear polarization of 13C nuclei in the thermal decomposition of organic peroxides. Chem. Phys. Lett. 1970, 5, 521−526. (12) Buchachenko, A. L.; Nikiforov, G. A. Isotope fractionation induced by magnetic interactions. Doklady Akad. Nauk SSSR 1976, 228, 379−382. (13) Salikhov, K. M. Magnetic Isotope Effect in Radical Reactions; Springer-Verlag: Wien, 1996. (14) Buchachenko, A. L. Magnetic Isotope Effect in Chemistry and Biochemistry; Nova Science Publishers: New York, 2009. (15) Buchachenko, A. L. Magnetic isotope effect: Nuclear spin control of chemical reactions. J. Phys. Chem. A 2001, 105, 9995− 10011. (16) Buchachenko, A. L. Magnetic field-dependent molecular and chemical processes in biochemistry, genetics and medicine. Russ. Chem. Rev. 2014, 83, 1−12. (17) Grissom, Ch. B. Magnetic Field Effects in Biology: A Survey of Possible Mechanisms with Emphasis on Radical-Pair Recombination. Chem. Rev. 1995, 95, 3−24. (18) Rodgers, C. T. Magnetic field effects in chemical systems. Pure Appl. Chem. 2009, 81, 19−43. (19) Lambert, N.; Chen, Y.-N.; Cheng, Y.-C.; Li, C.-M.; Chen, G.-Y.; Nori, F. Quantum biology. Nat. Phys. 2013, 9, 10−18. (20) Hore, P. J.; Mouritsen, H. The radical-pair mechanism of magneto-reception. Annu. Rev. Biophys. 2016, 45, 299−344. (21) Hore, P. J. Are biochemical reactions affected by weak magnetic fields? Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 1357−1358. (22) Buchachenko, A. L. Why magnetic and electromagnetic effects in biology are ambiguous and contradictory? Bioelectromagnetics 2016, 37, 1−13. (23) Buchachenko, A. L.; Kuznetsov, D. A.; Breslavskaya, N. N. Chemistry of enzymatic ATP synthesis: An insight through the isotope window. Chem. Rev. 2012, 112, 2042−2058. (24) Koplak, O.; Morgunov, R. B.; Buchachenko, A. L. Magnetic isotope and magnetic field effects on the silicon oxidation. Chem. Phys. Lett. 2013, 560, 29−31. 883
DOI: 10.1021/acs.accounts.6b00608 Acc. Chem. Res. 2017, 50, 877−884
Article
Accounts of Chemical Research 24
Mg-25Mg-26Mg isotope effect in mitochondrial ADP phosphorylation. Cell Biochem. Biophys. 2005, 43, 243−252. (48) Buchachenk, A. L.; Chekhonin, V. P.; Orlov, A. P.; Kuznetsov, D. A. Zinc-related magnetic isotope effect in the enzymatic ATP synthesis: a medicinal potential of the nuclear spin selectivity phenomena. Int. J. Mol. Med. Adv. Sci. 2010, 6, 34−37. (49) Buchachenko, A. L.; Kuznetsov, D. A.; Breslavskaya, N. N.; Shchegoleva, L. N.; Arkhangelsky, S. E. Calcium induced ATP synthesis: Isotope effect, magnetic parameters and mechanism. Chem. Phys. Lett. 2011, 505, 130−134. (50) Buchachenko, A. L.; Kouznetsov, D. A.; Arkhangelsky, S. E.; Orlova, M. A.; Markarian, A. A. Spin biochemistry: intra-mitochondrial nucleotide phosphorylation is a magnesium nuclear spin controlled process. Mitochondrion 2005, 5, 67−69. (51) Buchachenko, A. L.; Kouznetsov, D. A.; Orlova, M. A.; Markarian, A. A. Magnetic isotope effect of magnesium in phosphoglycerate kinase phosphorylation. Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 10793−10796. (52) Buchachenko, A. L.; Kouznetsov, D. A.; Breslavskaya, N. N.; Orlova, M. A. Magnesium isotope effect in enzymatic phosphorylation. J. Phys. Chem. B 2008, 112, 2548−2556. (53) Buchachenko, A. L.; Kouznetsov, D. A. Magnetic control of enzymatic phosphorylation. J. Phys. Chem. & Biophys 2014, 4, 142− 151. (54) Buchachenko, A. L.; Kuznetsov, D. A. Magnetic field affects enzymatic ATP synthesis. J. Am. Chem. Soc. 2008, 130, 12868−12869. (55) Svistunov, A. A.; Napolov, Y. K.; Bukhvostov, A. A.; Shatalov, O. A.; Alyautdin, R. N.; Kuznetsov, D. A. The mitochondria free iron content of limit an isotope effect of 25Mg2+ in ATP synthesis. Cell Biochem. Biophys. 2013, 66, 417−418. (56) Alberts, I. L.; Wang, Y.; Schlick, T. DNA polymerase β catalysis: are different mechanisms possible? J. Am. Chem. Soc. 2007, 129, 11100−11106. (57) Buchachenko, A. L.; Orlov, A. P.; Kuznetsov, D. A.; Breslavskaya, N. N. Magnetic Isotope and Magnetic Field Effects on the DNA Synthesis. Nucleic Acids Res. 2013, 41, 8300−8307. (58) Bukhvostov, A. A.; Shatalov, O. A.; Buchachenko, A. L.; Kouznetsov, D. A. Paramagnetic impact on DNA polymerase beta function. Der Pharmacia Lettre 2013, 5, 18−26. (59) Bukhvostov, A. A.; Shatalov, O. A.; Buchachenko, A. L.; Kouznetsov, D. A. The DNA Repair Key Enzyme Affected by 43Ca2+ ions. A New Platform for Anti-leukemia Therapies. British Journal of Pharmacology and Toxicology 2014, 5, 42−48. (60) Buchachenko, A. L.; Orlov, A. P.; Kuznetsov, D. A.; Breslavskaya, N. N. Magnetic control of the DNA synthesis. Chem. Phys. Lett. 2013, 586, 138−142.
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