Action Of Mg2 Research Articles

A Multifunctional DNA Nanoassembly for Cancer Cell Detection and Combined Gene-Chemotherapy Therapy.

Although DNAzyme is a promising gene therapy agent, low cellular uptake efficiency, poor biological stability, and the unsatisfactory effect of monotherapy limit its development. Herein, a multifunctional DNA nanoassembly (RCA product-aptamer-DNAzyme, RAD) was constructed for cancer cell detection and targeted delivery of doxorubicin (DOX) and DNAzyme. Briefly, the rolling circle amplification (RCA) product was employed as a scaffold, and each repeated sequence was designed to combine with three single-stranded DNA (ssDNA), which carried the aptamer AS1411 sequence, fluorescent group, and DNAzyme sequence, respectively. Up to 40 groups of ssDNA can be assembled into an RCA product, resulting in a high affinity for cancer cells and stronger fluorescent signals. Due to the high binding affinity, RAD displayed high sensitivity for the detection of HepG-2 cells (the limit of detection was 200 cells/mL). In addition, with the formation of the double helix structure, each RAD could load up to 200 DOX molecules. Subsequently, RAD could efficiently and selectively deliver DOX and DNAzyme into cancer cells through the multivalent interaction between the aptamers and membrane nucleolin. Then, the released DNAzyme could recognize and cleave survivin mRNA under the action of Mg2+, leading to the apoptosis of HepG-2 cells for gene therapy, while DOX inserted into intracellular DNA to inhibit cell proliferation, realizing chemotherapy. According to the results, RAD-DOX displayed enhanced therapeutic effects compared with individual gene therapy or chemotherapy, and RAD could protect membrane nucleolin-negative cells from the effects of DOX. Overall, given the enhanced serum stability, high drug-loading capacity, and excellent selective cellular uptake ability of RAD, this strategy shows great potential in the field of cancer therapy.

Understanding the mechanisms behind the antibacterial activity of magnesium hydroxide nanoparticles against sulfate-reducing bacteria in sediments

Nanomaterials, with their small size, surface characteristics, and antibacterial properties, are extensively employed across environmental, energy, biomedical, agricultural, and other industries. This study examined the antibacterial efficacy of magnesium hydroxide (Mg(OH)2) nanoparticles (NPs) against sulfate-reducing bacteria (SRB) within sediments. The inhibitory effects of two types of Mg(OH)2 NPs with distinct particle sizes (20.3 and 29.6 nm) and concentrations (0–10.0 mg/mL) were examined under optimal treatment conditions. The antibacterial mechanisms of Mg(OH)2 NPs through direct contact and dissolution effects were determined. The results revealed a correlation between the concentration, particle size, and inhibitory activity, with the smallest NPs (20.3 nm) at the highest concentration (10.0 mg/mL) substantially reducing SRB counts from 8.77 ± 0.18 to 6.48 ± 0.13 log10 colony forming units/mL after 6 h treatment. Treatment with high concentrations of Mg(OH)2 NPs induced cellular damage, reduced intracellular lactate dehydrogenase activity, and elevated intracellular catalase activity and H2O2 content, suggesting that the contact effect of NPs stimulated SRB. This leads to oxidative stress response and structural damage to the cell membrane, which has emerged as the primary driver of the antibacterial action of Mg(OH)2 NPs. This study presents a novel nanomaterial that can inhibit and control SRB in natural sedimentary environments.

Activating Effect of AlCl3 in Homocoupling Reaction of Acetylene Derivatives under the Action of Mg–Cp2ZrCl2 Reagent Systems

Activating Effect of AlCl3 in Homocoupling Reaction of Acetylene Derivatives under the Action of Mg–Cp2ZrCl2 Reagent Systems

Excellent High‐Rate Electrochemical Performances of Microspherical High‐Voltage Spinel Cathodes Synthesized by a Polyacrylamide‐Assisted Co‐Precipitation Method

A convenient strategy to construct microspherical LiNi0.5Mn1.5O4 (LNMO‐P) or Mg‐doped LiNi0.5Mn1.5O4 (LNMO‐P‐M) cathodes by polyacrylamide (PAAM)‐assisted coprecipitation is developed. Due to the coacervation effect of PAAM, the microspherical LNMO‐P and LNMO‐P‐M samples with small primary particle sizes and the uniform primary particles distribution are identified, resulting in a remarkable electrochemical performance with conventional electrolytes. The first coulomb efficiency of the LNMO‐P sample is enhanced to 84.7% and a high discharge capacity of 133.2 mAh g−1 is observed. Of significance, the LNMO‐P‐M sample prepared with PAAM shows excellent high‐rate electrochemical performance. Its capacity retention is 94.9% at the charge rate of 5C after 300 cycles and 95.3% at the discharge rate of 15C after 500 cycles. The improvement electrochemical performance of LNMO‐P‐M sample can be attributed to its strengthened crystal structure, moderate Mn3+ content by the action of Mg, and its improved uniform composition distribution caused by PAAM.

The Role of Magnesium in the Pathogenesis of Metabolic Disorders.

Magnesium (Mg) is an essential nutrient for maintaining vital physiological functions. It is involved in many fundamental processes, and Mg deficiency is often correlated with negative health outcomes. On the one hand, most western civilizations consume less than the recommended daily allowance of Mg. On the other hand, a growing body of evidence has indicated that chronic hypomagnesemia may be implicated in the pathogenesis of various metabolic disorders such as overweight and obesity, insulin resistance (IR) and type 2 diabetes mellitus (T2DM), hypertension (HTN), changes in lipid metabolism, and low-grade inflammation. High Mg intake with diet and/or supplementation seems to prevent chronic metabolic complications. The protective action of Mg may include limiting the adipose tissue accumulation, improving glucose and insulin metabolism, enhancing endothelium-dependent vasodilation, normalizing lipid profile, and attenuating inflammatory processes. Thus, it currently seems that Mg plays an important role in developing metabolic disorders associated with obesity, although more randomized controlled trials (RCTs) evaluating Mg supplementation strategies are needed. This work represents a review and synthesis of recent data on the role of Mg in the pathogenesis of metabolic disorders.

Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.

Magnesium (Mg) may have several beneficial effects on human health outcomes. One hypothesized mechanism eliciting such effects is the action of Mg on serum inflammatory parameters. However, studies on this topic to date have several important limitations. Therefore, the present systematic review and meta-analysis aimed to summarize the current state of the art of all randomized control trials (RCTs) investigating the effects of Mg supplementation versus placebo on serum parameters of inflammation. We searched several databases until 23 November 2021 for RCTs. Eligible studies were RCTs investigating the effect of oral Mg supplementation vs. placebo and having serum inflammatory markers as an outcome. Among 2484 papers initially screened, 17 randomized controlled trials (889 participants; mean age: 46 years; females: 62.5%) were included. Generally, a low risk of bias was present. In meta-analysis, Mg supplementation significantly decreased serum C reactive protein (CRP) and increased nitric oxide (NO) levels. In descriptive findings, Mg supplementation significantly reduced plasma fibrinogen, tartrate-resistant acid phosphatase type 5, tumor necrosis factor-ligand superfamily member 13B, ST2 protein, and IL-1. In conclusion, Mg supplementation may significantly reduce different human inflammatory markers, in particular serum CRP and NO levels.

Ratiometric determination of human papillomavirus-16 DNA by using fluorescent DNA-templated silver nanoclusters and hairpin-blocked DNAzyme-assisted cascade amplification.

A signal amplification method has been developed for determination of human papillomavirus-16 DNA (HPV-16 DNA). It consists of a combination of using (a) two-color emitting fluorescent DNA-templated silver nanoclusters (DNA-AgNCs); (b) hairpin-blocked DNAzyme probe (H-Dz), and (c) catalytic hairpin assembly. In the absence of the model target HPV-16 DNA, the H-Dz forms a hairpin structure through intramolecular hybridization. It inhibits the catalytic activity of the DNAzyme. However, in the presence of HPV-16 DNA, it will hybridize with the DNAzyme probe which leads to the opening of the hairpin and the formation of an active secondary structure in the catalytic core. This produces an "active" DNAzyme which can cut H-Dz under the catalytic action of Mg(II) ions. Then, the DNA fragment and HPV-16 DNA are separated due to the weak hybridization. The former triggers a downstream catalytic hairpin assembly (CHA). This changes the color of the fluorescence of DNA-AgNCs from red (630nm) to yellow (570nm). The HPV-16 DNA will hybridize with another H-Dz to trigger the next round of activation cycle to cut H-Dz. In this way, recycling amplification results in the generation of a strong signal that allows human HPV-16 DNA to be detected with a 5.7 pM detection limit. Graphical abstract A simple and effective cascade signal amplification method was developed for fluorometric determination of HPV-16 DNA. It is based on a combination of chameleon fluorescent DNA-AgNC, hairpin-blocked DNAzyme probe and catalytic hairpin assembly (CHA). Target recycling amplification results in significant signal changes, thus providing high detection sensitivity.

Role of Mono- and Divalent Ions in Peptide Glu-Asp-Arg-DNA Interaction.

The interaction of the regulatory biologically active peptide Glu-Asp-Arg (EDR) with DNA is considered by spectral, NMR, viscosimetry, and molecular dynamics methods. It was shown that EDR can partly penetrate into the major groove of DNA and affect the base atoms, mainly the N7 and O6 of guanine. It was observed that Mg2+ ions can promote DNA-EDR interaction due to their effective screening of the negatively charged phosphate groups of DNA. This action of Mg2+ remains in salted solution as well.

Inhibition of NF-κB pathway in fibroblast-like synoviocytes by α-mangostin implicated in protective effects on joints in rats suffering from adjuvant-induced arthritis

α-Mangostin (MG) is a bioactive compound isolated from mangosteen. This study was aimed to investigate effects of MG on adjuvant-induced arthritis (AA) in rats and decipher the underlying mechanisms. Clinical severity of AA was evaluated by paw oedema, arthritis score, and hematological parameters. Digital radiography (DR) and histological examinations were employed to assess joints destructions. Immune functions were evaluated by T cell subsets distribution. Effects on NF-κB pathway were investigated by immunohistochemical, western-blot and immunofluorescence methods both in vivo and vitro. It was found MG possessed superior anti-inflammatory effects in vivo, suggested by attenuated paw swelling, reduced inflammatory cells infiltration and decreased the secretion of TNF-α and IL-1β in serum. Meanwhile MG inhibited fibrous hyperplasia, synovial angiogenesis, cartilage and bone degradation in AA rats. Although MG exerted little effects on CD4+ population, it greatly decreased IFN-γ positive cells and promoted expression of FOXP3 in immune organs, indicating restoration of Th1/Treg cells ratio and recovery of immune homeostasis in vivo. Inhibition of NF-κB induced by MG was indicated by reduced the expression of p-p65 and VEGF in synovium. In vitro experiments found MG at 10 μg/ml significantly suppressed the expression and phosphorylation of key proteins implicated in NF-κB pathway and inhibited nucleus translocation of p65. These changes led to increased apoptosis and proliferation inhibition of HFLS-RA cells. The results demonstrated regulation of immune functions was deeply involved in the therapeutic actions of MG on AA, and it's inhibition on NF-κB in fibroblast-like synoviocytes was associated to the protective effects on joints.

A recent intermezzo at the Ribosome Club.

Two sets of ribosome structures have recently led to two different interpretations of what limits the accuracy of codon translation by transfer RNAs. In this review, inspired by this intermezzo at the Ribosome Club, we briefly discuss accuracy amplification by energy driven proofreading and its implementation in genetic code translation. We further discuss general ways by which the monitoring bases of 16S rRNA may enhance the ultimate accuracy (d-values) and how the codon translation accuracy is reduced by the actions of Mg2+ ions and the presence of error inducing aminoglycoside antibiotics. We demonstrate that complete freezing-in of cognate-like tautomeric states of ribosome-bound nucleotide bases in transfer RNA or messenger RNA is not compatible with recent experiments on initial codon selection by transfer RNA in ternary complex with elongation factor Tu and GTP. From these considerations, we suggest that the sets of 30S subunit structures from the Ramakrishnan group and 70S structures from the Yusupov/Yusupova group may, after all, reflect two sides of the same coin and how the structurally based intermezzo at the Ribosome Club may be resolved simply by taking the dynamic aspects of ribosome function into account.This article is part of the themed issue ‘Perspectives on the ribosome’.

Chromium determination in food by slurry sampling graphite furnace atomic absorption spectrometry using classical and permanent modifiers

A simple method, using permanent modifiers, has been developed for chromium (Cr) determination in food of plant origin by the slurry sampling graphite furnace atomic absorption spectrometry. In particular comparison of the action of Mg(NO3)2, iridium (Ir)/niobium (Nb) and iridium (Ir)/tungsten (W) was examined. Finally, for chromium determination in food, the mixture of 2μg of Ir with 10μg of Nb was used as permanent modifier. The analytical procedure was optimised carefully on the basis of the data from pyrolysis and atomisation temperature curves studies. The results obtained for four certified reference materials using external calibration with aqueous standards were in good agreement with the certified values. The precision and accuracy of Cr determination by the described method were also acceptable: the RSD were lower than 10% and recoveries for CRMs were in the range of 95–103%. The characteristic mass for chromium was determined to be 3.9pg and the detection limit for the optimised procedure at the 0.75% (w/v) slurry concentration – 86.6ngg−1.

Dysregulation of renal transient receptor potential melastatin 6/7 but not paracellin-1 in aldosterone-induced hypertension and kidney damage in a model of hereditary hypomagnesemia

Hyperaldosteronism, important in hypertension, is associated with electrolyte alterations, including hypomagnesemia, through unknown mechanisms. To test whether aldosterone influences renal Mg(2+) transporters, (transient receptor potential melastatin (TRPM) 6, TRPM7, paracellin-1) leading to hypomagnesemia, hypertension and target organ damage and whether in a background of magnesium deficiency, this is exaggerated. Aldosterone effects in mice selectively bred for high-normal (MgH) or low (MgL) intracellular Mg(2+) were studied. Male MgH and MgL mice received aldosterone (350 μg/kg per day, 3 weeks). SBP was elevated in MgL. Aldosterone increased blood pressure and albuminuria and increased urinary Mg(2+) concentration in MgH and MgL, with greater effects in MgL. Activity of renal TRPM6 and TRPM7 was lower in vehicle-treated MgL than MgH. Aldosterone increased activity of TRPM6 in MgH and inhibited activity in MgL. TRPM7 and paracellin-1 were unaffected by aldosterone. Aldosterone-induced albuminuria in MgL was associated with increased renal fibrosis, increased oxidative stress, activation of mitogen-activated protein kinases and nuclear factor-NF-κB and podocyte injury. Mg(2+) supplementation (0.75% Mg(2+)) in aldosterone-treated MgL normalized plasma Mg(2+), increased TRPM6 activity and ameliorated hypertension and renal injury. Hence, in a model of inherited hypomagnesemia, TRPM6 and TRPM7, but not paracellin-1, are downregulated. Aldosterone further decreased TRPM6 activity in hypomagnesemic mice, a phenomenon associated with hypertension and kidney damage. Such effects were prevented by Mg(2+) supplementation. Amplified target organ damage in aldosterone-induced hypertension in hypomagnesemic conditions is associated with dysfunctional Mg(2+)-sensitive renal TRPM6 channels. Novel mechanisms for renal effects of aldosterone and insights into putative beneficial actions of Mg(2+), particularly in hyperaldosteronism, are identified.

Timing, location and crop species influence the magnitude of amelioration of aluminum toxicity by magnesium

The protective effect of cations, especially Ca and Mg, against aluminum (Al) rhizotoxicity has been extensively investigated in the last decades. The mechanisms by which the process occurs are however only beginning to be elucidated. Six experiments were carried out here to characterize the protective effect of Mg application in relation to timing, location and crop specificity: Experiment 1 - Protective effect of Mg compared to Ca; Experiment 2 - Protective effect of Mg on distinct root classes of 15 soybean genotypes; Experiment 3 - Effect of timing of Mg supply on the response of soybean cvs. to Al; Experiment 4 - Investigating whether the Mg protective effect is apoplastic or simplastic using a split-root system; Experiment 5 - Protective effect of Mg supplied in solution or foliar spraying, and Experiment 6 - Protective effect of Mg on Al rhizotoxicity in other crops. It was found that the addition of 50 mmol L-1 Mg to solutions containing toxic Al increased Al tolerance in 15 soybean cultivars. This caused soybean cultivars known as Al-sensitive to behave as if they were tolerant. The protective action of Mg seems to require constant Mg supply in the external medium. Supplying Mg up to 6 h after root exposition to Al was sufficient to maintain normal soybean root growth, but root growth was not recovered by Mg addition 12 h after Al treatments. Mg application to half of the root system not exposed to Al was not sufficient to prevent Al toxicity on the other half exposed to Al without Mg in rooting medium, indicating the existence of an external protection mechanism of Mg. Foliar spraying with Mg also failed to decrease Al toxicity, indicating a possible apoplastic role of Mg. The protective effect of Mg appeared to be soybean-specific since Mg supply did not substantially improve root elongation in sorghum, wheat, corn, cotton, rice, or snap bean when grown in the presence of toxic Al concentrations.

Novobiocin inhibits the self-splicing of the primary transcripts of T4 phage thymidylate synthase gene

Effects of the antibiotic novobiocin on the self-splicing of primary transcripts of the phage T4 thymidylate synthase gene (td) have been investigated. Novobiocin at 10 mM concentration inhibited the splicing by about 5% but at 40 mM concentration the splicing rate was inhibited by about 50%. The novobiocin inhibition of the self-splicing reaction was not reversed even at a high concentration (200 microM) of guanosine. However, increasing the Mg(2+) ion concentrations up to 20 mM almost fully restored the splicing activity to the normal splicing level. The double reciprocal plot analysis demonstrated that novobiocin acts as a mixed noncompetitive inhibitor for the td intron RNA with a K (i) of 90 mM. The splicing inhibition by novobiocin was strongly dependent on Mg(2+) ion concentration, indicating electrostatic interactions with the td intron RNA. It is likely that the antibiotic novobiocin may interfere with the catalytic actions of Mg(2+) ion in the splicing reaction of the td intron RNA.

Mg2+ and memantine block of rat recombinant NMDA receptors containing chimeric NR2A/2D subunits expressed in Xenopus laevis oocytes

N-methyl-d-aspartate receptors (NMDARs) display differences in their sensitivity to the channel blockers Mg(2+) and memantine that are dependent on the identity of the NR2 subunit present in the receptor-channel complex. This study used two-electrode voltage-clamp recordings from Xenopus laevis oocytes expressing recombinant NMDARs to investigate the actions of Mg(2+) and memantine at the two NMDARs displaying the largest differences in sensitivity to these blockers, namely NR1/NR2A and NR1/NR2D NMDARs. In addition, NR2A/2D chimeric subunits have been employed to examine the effects of pore-forming elements and ligand-binding domains (LBD) on the potency of the block produced by each of these inhibitors. Our results show that, as previously documented, NR2D-containing NMDARs are less sensitive to voltage-dependent Mg(2+) block than their NR2A-containing counterparts. The reduced sensitivity is determined by the M1M2M3 membrane-associated regions, as replacing these regions in NR2A subunits with those found in NR2D subunits results in a approximately 10-fold reduction in Mg(2+) potency. Intriguingly, replacing the NR2A LBD with that from NR2D subunits results in a approximately 2-fold increase in Mg(2+) potency. Moreover, when responses mediated by NR1/NR2A NMDARs are evoked by the partial agonist homoquinolinate, rather than glutamate, Mg(2+) also displays an increased potency. Memantine block of glutamate-evoked currents is most potent at NR1/NR2D NMDARs, but no differences are observed in its ability to inhibit NR2A-containing or NR2A/2D chimeric NMDARs. We suggest that the potency of block of NMDARs by Mg(2+) is influenced not only by pore-forming regions but also the LBD and the resulting conformational changes that occur following agonist binding.

The mapping class group action on the homology of the configuration spaces of surfaces

In this paper, we study the natural action of the mapping class group ℳg, 1 on the (co)homology groups of the configuration spaces of n-points on a surface Σ of genus g with the boundary ∂Σ ≅ S1. We present two main results in this paper. The first result is that the kernel of the action of ℳg, 1 coincides with the kernel of the natural action on the nth lower central quotient group of the fundamental group of Σ. The second result is a new interpretation of the cohomology group H*(ℳg, 1; T[H1]) of ℳg, 1 with coefficients in the free tensor algebra T[H1] over ℤ generated by the first homology group H1 of Σ, by using the configuration spaces. More precisely, we define a certain cochain complex C of ℳg, 1-modules by using the configuration spaces and prove that H*(ℳg, 1; C) is canonically isomorphic to H*(ℳg, 1; T[H1]).

Magnesium cation initiates nucleoside triphosphate to monophosphate conversion by a radical mechanism: Quantum molecular dynamics simulation

A DFT:B3LYP (6-311G** basis set) quantum molecular dynamics simulation was used to study the mechanism of Mg2+-induced conversion of guanosine triphosphate (GTP) to guanosine monophosphate (GMP). The computations were performed at 310 K in a bath of 178 water molecules surrounding the Mg(H2O)2-GTP complex and mimicking the hydration shells. Dissociation of the Mg2+-GTP complex (process duration, 5 ps) produces two phosphate anions (Pi), a hydrated Mg2+ cation, atomic oxygen, and a highly reactive GMP radical. This radical appears as a result of the action of Mg2+, which initiates the radical mechanism of GTP cleavage. At the initial stage of the interaction with GTP, Mg2+ is reduced to Mg+, producing an ion-radical pair +Mg·-·GTP3−. In the absence of Mg2+, an inert GMP molecule forms instead of the GMP radical as a result of hydrolytic cleavage of GTP via an ionic mechanism. Presumably, formation of the GMP radical and analogous radicals with adenosine, cytidine, thymidine, and uridine is a key point in the syntheses of deoxyribonucleic and ribonucleic acids.

Defective Mg 2+ regulation of RyR1 as a causal factor in malignant hyperthermia

In skeletal muscle, Mg 2+ exerts a dual inhibitory effect on RyR1, by competing with Ca 2+ at the activation site and binding to a low affinity Ca 2+/Mg 2+ inhibitory site. Pharmacological activators of RyR1 must overcome the inhibitory action of Mg 2+ before Ca 2+ efflux can occur. In normal muscle, where the free [Mg 2+] i is ∼1 mM, even prolonged exposure to millimolar levels of volatile anesthetics does not initiate SR Ca 2+ release. However, when the cytosolic [Mg 2+] is reduced below the physiological range, low levels of volatile anesthetic within the clinically relevant range (⩽1 mM) can initiate SR Ca 2+ release, in the form of a propagating Ca 2+ wave. In human muscle fibers from malignant hyperthermia susceptible patients, such Ca 2+ waves occur when 1 mM halothane is applied at physiological [Mg 2+] i. There is increasing evidence to suggest that defective Mg 2+ regulation of RyR1 confers susceptibility to malignant hyperthermia. At the molecular level, interactions between critical RyR1 subdomains may explain the clustering of RyR1 mutations and associated effects on Mg 2+ regulation.

Magnesium Deficiency Enhances Hydrogen Peroxide Production and Oxidative Damage in Chick Embryo Hepatocyte In Vitro

Magnesium deficiency and oxidative stress have been identified as correlative factors in many diseases. The origin of free radicals correlated with oxidative damage resulting from Mg-deficiency is unclear at the cellular level. To investigate whether hydrogen peroxide (H2O2) is associated in the oxidative stress induced by Mg-deficiency, the effect of Mg2+ deficiency (0, 0.4, 0.7 mM) on the metabolism of H2O2 was investigated in cultured chick embryo hepatocytes. After being cultured in the media with various concentrations of Mg2+ for 1, 2, 4, 6 and 10 days, parameters of H2O2 production, catalase activity, lipid peroxidation, intracellular total Mg and cell viability were analyzed. Results demonstrated that long-term incubation of chick embryo hepatocyte in extracellular Mg2+-deprivative and Mg2+-deficient (0.4 mM) states significantly enhanced the production of H2O2 (approximately twofold, respectively) and lipid peroxidation in the cell cultures, while decreasing the cell viability. Additionally, the reversing action of Mg2+ re-added to 1.0 mM and the partial reversing action of dimethylthiourea suggested that (i) [Mg2+]e deficiency induced the increase of H2O2 production, (ii) [Mg2+]e deficiency decreased catalase activity in chick embryo hepatocyte in vitro, subsequently causing oxidative stress and cell peroxidative damage.

Molecular dynamics DFT:B3LYP study of guanosinetriphosphate conversion into guanosinemonophosphate upon Mg2+ chelation of ? and ? phosphate oxygens of the triphosphate tail

A molecular dynamics DFT:B3LYP (6-31G(**) basis set) study is used to elucidate the mechanism of guanosinetriphosphate (GTP) conversion into guanosinemonophosphate (GMP) upon the action of Mg(2+) (magnesium cofactor). The computations are carried out at 310 K in a volume of 178 water molecules, which surround the Mg(2+)-GTP complex and imitate the effect of solution. Over 5 ps, Mg(2+)-GTP appears to be fully decomposed, yielding five final products: two hydrated molecules of inorganic phosphate Pi, a hydrated Mg(2+), atomic oxygen (which in the course of a couple of subsequent reactions gains two hydrogens and converts into a water molecule) and a highly active *GMP radical. The radical production is linked to presence of Mg(2+), which initiates a radical mechanism of GTP cleavage. At the initial stage, Mg(2+) undergoes reduction to Mg(+), accompanied by the formation of an ion-radical pair with GTP, (+)Mg*-*GTP(3-). Without Mg(2+), an inert form of GMP (the ionic mechanism of GTP hydrolytic cleavage) rather than GMP is produced. *GMP production, which is similar to that of *AMP (adenosinemonophosphate), *CMP (cytidinemonophosphate), TMP (thymidinemonophosphate) and *UMP (uridinemonophosphate), plays a crucial role in DNA and RNA single chain synthesis.