Inorganic Pharmacology of Lithium

Birch, Nicholas J.

doi:10.1021/cr9804240

Cited by 93 publications

(55 citation statements)

References 262 publications

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“…[1] Therefore, detailed understanding of fundamental reactions of solvated lithium cations, for example ligand-exchange reactions in different solvents, is essential.…”

Section: Introductionmentioning

confidence: 99%

Ligand‐Exchange Processes on Solvated Lithium Cations: DMSO and Water/DMSO Mixtures

et al. 2007

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Solutions of LiClO(4) in solvent mixtures consisting of dimethylsulfoxide (DMSO) and water, or DMSO and gamma-butyrolactone, were studied by (7)Li NMR spectroscopy (for complexation by cryptands in gamma-butyrolactone as a solvent, see: E. Pasgreta, R. Puchta, M. Galle, N. J. R. van Eikema Hommes, A. Zahl, R. van Eldik, J. Incl. Phen., 2007, 58, 81-88). Chemical shifts indicate that the Li(+) ion is coordinated by four DMSO molecules. In the binary solvent mixture of water and DMSO, no selective solvation is detected, thus indicating that on increasing the water content of the solvent mixture, DMSO is gradually displaced by water in the coordination sphere of Li(+). The ligand-exchange mechanism of Li(+) ions solvated by DMSO and water/DMSO mixtures was studied using DFT calculations. Ligand exchange on [Li(DMSO)(4)](+) was found to follow a limiting associative (A) mechanism. The displacement of coordinated H(2)O by DMSO in [Li(H(2)O)(4)](+) follows an associative interchange mechanism. The suggested mechanisms are discussed in reference to available experimental and theoretical data.

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“…[1] Therefore, detailed understanding of fundamental reactions of solvated lithium cations, for example ligand-exchange reactions in different solvents, is essential.…”

Section: Introductionmentioning

confidence: 99%

Ligand‐Exchange Processes on Solvated Lithium Cations: DMSO and Water/DMSO Mixtures

et al. 2007

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“…Several hypotheses for its mechanism of action have been advanced [1][2][3]. One main branch of the research into the Li þ mechanism of action has focused on the effect of Li þ on guanine-nucleotide binding (G) proteins.…”

Section: Introductionmentioning

confidence: 99%

Competition between lithium and magnesium ions for the G-protein transducin in the guanosine 5 ′ -diphosphate bound conformation

Srinivasan

Toon

Amari

et al. 2004

Journal of Inorganic Biochemistry

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Liþ is the most effective drug used to treat bipolar disorder; however, its exact mechanism of action has yet to be elucidated. One hypothesis is that Li þ competes with Mg 2þ for the Mg 2þ binding sites on guanine-nucleotide binding proteins (G-proteins). Using 7 Li T 1 relaxation measurements and fluorescence spectroscopy with the Mg 2þ fluorophore furaptra, we detected Li þ /Mg 2þ competition in three preparations: the purified G-protein transducin (G t ), stripped rod outer segment membranes (SROS), and SROS with purified G t reattached (ROS-T). When purified ROS-T, SROS or transducin were titrated with Li þ in the presence of fixed amounts of Mg 2þ , the apparent Li þ binding constant decreased due to Li þ /Mg 2þ competition. Whereas for SROS the competition mechanism was monophasic, for G t , the competition was biphasic, suggesting that in G t , Li þ /Mg 2þ competition occurred with different affinities for Mg 2þ in two types of Mg 2þ binding sites. Moreover, as [Li þ ] increased, the fluorescence excitation spectra of both ROS-T and G t were blue shifted, indicating an increase in free [Mg 2þ ] compatible with Li þ displacement of Mg 2þ from two low affinity Mg 2þ binding sites of G t . G t release from ROS-T membrane was also inhibited by Li þ addition. In summary, we found evidence of Li þ /Mg 2þ competition in G t -containing preparations.

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“…It is more reactive than gold and less reactive than copper. There are two stable isotopes, 107 Ag (51.82% abundance) and 109 Ag (48.18% abundant). Both are NMR active with nuclear spins, I = 1/2, and have reasonable receptivity.…”

Section: The Element and Ionmentioning

confidence: 99%

“…107 The kidney, thyroid, and adrenal glands accumulate between 0.3 and 0.4 mmol kg −1 wet weight, while the brain concentrations are somewhat below 0.2 mmol kg −1 wt weight. 107 Oral dosing of patients with lithium carbonate (250 mg in previously untreated subjects) leads to plasma levels of ca. 0.2 mmol L −1 after 1 to 4 hours, followed by a decay over the next 72 hours (Figure 18).…”

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confidence: 99%

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Metal‐Based Drugs

Shaw

2005

Encyclopedia of Inorganic Chemistry

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Metallopharmaceuticals have a long history in the development of chemotherapy. The more recent success of cisplatin and six related Pt‐based antitumor drugs, and longer histories of chrysotherapy (gold treatments) for arthritis, bismuth antiulcer agents, and silver‐, antimony‐ and arsenic‐based antimicrobial agents demonstrate that the periodic table represents a potential wealth of medicinal agents to be explored and developed in the future. This article reviews the use of twelve elements (Ag, As, Au, Bi, Ga, Li, Pt, Ru, Sb, Sn, Ti, V) for a wide variety of diseases and disorders. The current state of research on particular applications varies widely – from promising treatments that have not yet reached the clinic to those that are well established empirically despite uncertain mechanisms of action. The array of antitumor agents licensed or in clinical trials includes compounds of As, Ga, Ru, and Ti, in addition to platinum. There are also exciting efforts to apply known treatments or biological properties to new diseases by taking advantage of extensive databases, for example, developing antitumor agents from organotin complexes that have long been used as fungicides and antifouling agents, and antimicrobial agents from gold complexes. The ability to modulate the properties of metal complexes by choice of the oxidation state (Au I vs Au III ; Pt II vs Pt IV ; V III , V IV & V V , etc.) and design of the medical carrier ligands (e.g. 1,2‐diaminocyclohexane vs two ammine ligands for Pt antitumor agents) allows targeting of particular tissues or cells and balancing of lipophilicity, solubility, and reactivity to balance therapeutic activity against toxicity. Many, if not most, metallopharmaceuticals are prodrugs that undergo redox changes and/or ligand exchange reactions in vivo to generate the active species. Hence, research on metallodrug metabolism and pharmacology is as important as the initial medicinal screening of the agents.

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Inorganic Pharmacology of Lithium

Cited by 93 publications

References 262 publications

Ligand‐Exchange Processes on Solvated Lithium Cations: DMSO and Water/DMSO Mixtures

Ligand‐Exchange Processes on Solvated Lithium Cations: DMSO and Water/DMSO Mixtures

Competition between lithium and magnesium ions for the G-protein transducin in the guanosine 5 ′ -diphosphate bound conformation

Metal‐Based Drugs

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