The Effect of Phenyl Substituents on 13C NMR Shifts and Metal Ions Binding to 4-Phenyl-2,4-Dioxobutanoic Acid Derivatives

Verbić, Tatjana Ž.; Drakulić, Branko J.; Zloh, Mire; Juranić, Ivan O.

doi:10.2174/157017808786857589

Cited by 5 publications

(9 citation statements)

References 33 publications

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“…The synthesis and characterisation of 1-7, 13-19 was previously reported. [6,7] Characterisation data for 8-12…”

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confidence: 99%

“…[10] We reported the influence of the phenyl substitution pattern in aryldiketo acids on Mg 2 + complexation. [7] In a similar manner, Mg 2 + bound to the fluoroquinolone carboxylic acid group at position 3 is necessary for the interaction with prokaryotic gyrase A (GyrA). [11] Furthermore, structural similarity between 1-20 and norfloxacin 21 was observed by overlaying the representative conformations of the monoanions of 1-20 generated by OMEGA, [12] with the representative conformations of 21 in its zwitterionic form, using ROCS.…”

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confidence: 99%

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Aryldiketo Acids Have Antibacterial Activity Against MDR Staphylococcus aureus Strains: Structural Insights Based on Similarity and Molecular Interaction Fields

Drakulić¹,

Stavri²,

Gibbons³

et al. 2009

ChemMedChem

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“…The synthesis and characterisation of 1-7, 13-19 was previously reported. [6,7] Characterisation data for 8-12…”

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confidence: 99%

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confidence: 99%

Aryldiketo Acids Have Antibacterial Activity Against MDR Staphylococcus aureus Strains: Structural Insights Based on Similarity and Molecular Interaction Fields

Drakulić¹,

Stavri²,

Gibbons³

et al. 2009

ChemMedChem

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“…15 It was shown that 4-aryl-2,4-dioxobutanoic acids (aryldiketo acids, ADKs) exert promising activity against multidrug resistant bacteria. 16 Herein, as a continuation of work on structure-property relationship studies 17,18 and the biological activity of ADKs, 16 the effects of pH on electronic properties of nine congeners (compounds 1-9, Fig. 1) were investigated using cyclic voltammetry (CV), and differential pulse polarography (DPP).…”

Section: Introductionmentioning

confidence: 99%

“…It was shown that this moiety is responsible for the inhibitory activity of ADKs since it is involved in interactions with metal ions within active sites of target enzymes. 18 The substitution pattern on the phenyl ring was systematically varied, yielding a set having different torsion between phenyl ring and the aryl keto group (Ar-C(O)). Due to the presence of ortho-Me groups and tri-and tetra-Me-substitution at the phenyl ring for some compounds, different congeners most probably differently approach and interact with the electrode.…”

Section: Introductionmentioning

confidence: 99%

Redox properties of alkyl-substituted 4-aryl-2,4-dioxobutanoic acids

Cvijetić¹,

Verbić

Drakulić

et al. 2017

JSCS

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Redox properties of a set of aryldiketo acids (ADKs), small organic molecules that comprise 2,4-dioxobutanoic acid moiety, were studied. Along with well-known HIV-1 integrase (IN) inhibition, ADKs exert widespread biological activities. The aim of this work was to evaluate the effects of aryl substitutions on the properties of the dioxobutanoic moiety that is involved in key interactions with metal ions within the active sites of target enzymes. The effect of pH on the electronic properties of nine congeners was examined using cyclic voltammetry and differential pulse polarography. The compounds were chosen as a simple set of congeners bearing Me-groups on the phenyl ring, which should not be involved in electrochemical reactions, leaving the diketo moiety as the sole electrophore. The substitution pattern was systematically varied, yielding a set having different torsion between the phenyl ring and the aryl keto group (Ar-C(O)). The protonation state of the ADKs at different pH values was determined from the experimentally obtained pK a values. The results showed that an equal number of protons and electrons were involved in the oxidation and reduction reactions at the surface of the electrode. Quantitative linear correlations were found between the reduction potentials and the energies of the frontier orbitals, calculated for neutral, mono-anionic and the corresponding radical anionic species, and the steric parameter as two independent variables.

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“…ADKs simultaneously exist in two enolate forms (Scheme 1, I and III), conformationally locked by the pseudo-ring, and one diketo form (II) having two rotatable bonds responsible for their conformational flexibility [15,17]. As a continuation of our group's work on structureproperty relationships [18][19][20] and biological activities of ADKs [6], we aimed to further explore their tautomeric preferences.…”

Section: Introductionmentioning

confidence: 99%

Tautomerism of 4-phenyl-2,4-dioxobutanoic acid. Insights from pH ramping NMR study and quantum chemical calculations

Cvijetić¹,

Pešić

Todorov

et al. 2017

Struct Chem

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Aryldiketo acids (ADKs) exhibit the variety of biological activities, mainly due to large affinity toward divalent metal ions. Metal complexation ability of ADKs, as well as interactions with proteins, depend on tautomeric form present in solution. The main aim of this study was to fully explore the tautomeric preferences of 4-phenyl-2,4-dioxobutanoic acid (4PDA), as ADKs representative, in aqueous media at different pH values. 1D and 2D NMR spectroscopy in combination with quantum chemical calculations was applied in order to better understand the tautomeric preferences of 4PDA. The data in highly acidic media are especially interesting since there are no such findings in the literature due to low solubility of ADKs in molecular form. At low pH values, where 4PDA is unionized, the most abundant tautomeric form is enol with keto group closer to phenyl ring. At higher pH values, mixture of two 4PDA ionic forms coexists in solution. Their ratio calculated according to NMR data fits the values predicted using two experimentally determined pKa values. Based on the complexity of 1 H NMR spectrum of monoanionic 4PDA form, coexistence of two stable rotamers was assumed. In an alkaline media 4PDA is mostly present in dianionic form. As π-electrons of dianion are delocalized over an entire keto-enol moiety, spectral distinction between tautomers was not possible. Quantum chemical calculations were used to predict relative stability of tautomers. The predictions were in good accordance with experimental results only in case when explicit water molecule was included in calculations.

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The Effect of Phenyl Substituents on 13C NMR Shifts and Metal Ions Binding to 4-Phenyl-2,4-Dioxobutanoic Acid Derivatives

Cited by 5 publications

References 33 publications

Aryldiketo Acids Have Antibacterial Activity Against MDR Staphylococcus aureus Strains: Structural Insights Based on Similarity and Molecular Interaction Fields

Aryldiketo Acids Have Antibacterial Activity Against MDR Staphylococcus aureus Strains: Structural Insights Based on Similarity and Molecular Interaction Fields

Redox properties of alkyl-substituted 4-aryl-2,4-dioxobutanoic acids

Tautomerism of 4-phenyl-2,4-dioxobutanoic acid. Insights from pH ramping NMR study and quantum chemical calculations

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