Macroscopic and microscopic ionization constants of the thiol and amine groups in 1-methyl-4-mercaptopiperidine

Barrera, H.; Bayón, J. Carles; González-Duarte, Pilar; Sola, Joan; Vives, Josep

doi:10.1016/0039-9140(83)80127-1

Cited by 5 publications

(2 citation statements)

References 10 publications

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“…1 as ''analogue molecules'' column). That is, scaffold SC1 is structurally similar to aminobenzenethiol, a molecule that exhibits very strong chelating properties [25], in which the thiol group has been modified to a tioether to avoid the oxidation to disulfide. Scaffold SC2 is analogue to clioquinol (HCQ), a drug that has exhibited a metal-sequestering behavior in Ab deposits with relative success [26], in which the donor OH group has been substituted by a tioether group.…”

Section: Resultsmentioning

confidence: 99%

In silico strategies for the selection of chelating compounds with potential application in metal-promoted neurodegenerative diseases

Rodríguez‐Rodríguez

Rimola

Alí‐Torres

et al. 2010

J Comput Aided Mol Des

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The development of new strategies to find commercial molecules with promising biochemical features is a main target in the field of biomedicine chemistry. In this work we present an in silico-based protocol that allows identifying commercial compounds with suitable metal coordinating and pharmacokinetic properties to act as metal-ion chelators in metal-promoted neurodegenerative diseases (MpND). Selection of the chelating ligands is done by combining quantum chemical calculations with the search of commercial compounds on different databases via virtual screening. Starting from different designed molecular frameworks, which mainly constitute the binding site, the virtual screening on databases facilitates the identification of different commercial molecules that enclose such scaffolds and, by imposing a set of chemical and pharmacokinetic filters, obey some drug-like requirements mandatory to deal with MpND. The quantum mechanical calculations are useful to gauge the chelating properties of the selected candidate molecules by determining the structure of metal complexes and evaluating their stability constants. With the proposed strategy, commercial compounds containing N and S donor atoms in the binding sites and capable to cross the BBB have been identified and their chelating properties analyzed.

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Section: Resultsmentioning

confidence: 99%

In silico strategies for the selection of chelating compounds with potential application in metal-promoted neurodegenerative diseases

Rodríguez‐Rodríguez

Rimola

Alí‐Torres

et al. 2010

J Comput Aided Mol Des

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“…In the case of Cys, it can be concluded, as in previous theoretical calculations, [34] that the thiol group is less acidic than the amine group; the opposite has been reported. [35] A gross estimation of the bias in the solvation energy for divalent ions could be calculated taking into account the pKa values of Cys: the pKa difference between experimental and calculated values is ca. 2, which implies an overestimation of the solvation energies of c. a.…”

Section: Resultsmentioning

confidence: 99%

Unravelling the mechanism of intracellular oxidation of thiols by (N‐Cl)‐Taurine

Fernández

García

Armesto

et al. 2013

J of Physical Organic Chem

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Myeloperoxidase, a heme enzyme stored in high amounts in neutrophils and monocytes, produces reactive oxygen species that are involved in the innate mammalian response to infection; among these, the most reactive is HOCl, generated by oxidation of Cl À in the presence of H 2 O 2 . This powerful oxidant reacts very fast with protein side chains and peptide bonds. Taurine ( À O 3 SCH 2 CH 2 NH 3 + ), present in high concentrations in human neutrophils, traps the HOCl to yield (N-Cl)-Taurine, much less toxic and reactive; it is a long-lived oxidant which contributes to the killing of pathogenic organisms and plays a role in the inflammatory response. Kinetic data suggest that (N-Cl)-Tau reacts with cysteine and glutathione, two relevant thiols in mammals, via two pathways: direct oxidation (chlorination) of the thiolate by (N-Cl)-Tau involving general-acid catalysis, and, the major one, (N-Cl)-Tau hydrolysis followed by fast chlorine transfer from the so-formed HOCl/ClO À mixture to the corresponding thiolate, despite the highly unfavorable hydrolysis equilibrium (K H =10 À8 M). Scavenging of HOCl by strong nucleophiles like thiolates opens an effective reactive channel. Theoretical calculations, at the B3LYP/6-311++G(d,p) level of theory and using the SMD model to simulate aqueous salvation, agree with the experimental behavior, predicting that both the chlorine and the proton are almost half transferred at the transition state in the direct, general-acid catalyzed, chlorination of the thiolate by (N-Cl)-Tau. Under physiological conditions, the hydrolysis of (N-Cl)-Tau is the main responsible of the oxidation of intracellular thiols far away from the site of HOCl enzymatic production.

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Polynuclear thiolate complexes in solution. Solution equilibria studies of silver(I) complexes of 3-(dimethylamino)propane-1-thiol and 3-aminopropane-1-thiol and comparative study with 4-mercapto-1-methylpiperidine

González-Duarte¹,

Vives²

1990

J. Chem. Soc., Dalton Trans.

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Macroscopic and microscopic ionization constants of the thiol and amine groups in 1-methyl-4-mercaptopiperidine

Cited by 5 publications

References 10 publications

In silico strategies for the selection of chelating compounds with potential application in metal-promoted neurodegenerative diseases

In silico strategies for the selection of chelating compounds with potential application in metal-promoted neurodegenerative diseases

Unravelling the mechanism of intracellular oxidation of thiols by (N‐Cl)‐Taurine

Polynuclear thiolate complexes in solution. Solution equilibria studies of silver(I) complexes of 3-(dimethylamino)propane-1-thiol and 3-aminopropane-1-thiol and comparative study with 4-mercapto-1-methylpiperidine

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