“…Considering the 1 : 1 complexes in the higher protonation states (A-C), the B and C species are significantly more stable than chelate A. Additionally, and taking into account the experimental uncertainty in the log b values, the calculated stability values of B and C are in agreement with the reported experimental value. This reveals that PM acts as a monodentate ligand at low pH since the Cu 2+ competes against the protons for binding the amino and phenol groups, which supports the suppositions of El-Ezaby et al 68 The pK a values of the complexes calculated according to the reactions of eqn ( 9) and ( 12) (pK a (I) and pK a (II)) are reported in Table 3. In the case of complexes D, F and G, the pK a predictions show good agreement with the experimental values and allow the identification of the acidic groups with the pyridine nitrogen atoms.…”
Section: Stability Constants and Pk A Values Of Pm-cu Complexessupporting
confidence: 84%
“…The reported experimental log b values easily show differences of 0.5-1.5 log units, or even up to several log units in some extreme cases. 61,62,66,68 Therefore, the error in the log b value of the reference complex contributes significantly to the final error in the predicted stability constants. On the other hand, considering the magnitude of the experimental uncertainties, the log b values predicted with the proposed methodology match the precision of experiment.…”
Section: Theoretical Calculation Of Stability Constants Of Metal Comp...mentioning
Accurate prediction of thermodynamic constants of chemical reactions in solution is one of the current challenges in computational chemistry. We report a scheme for predicting stability constants (log β) and pKa values of metal complexes in solution by means of calculating free energies of ligand- and proton-exchange reactions using Density Functional Theory calculations in combination with a continuum solvent model. The accuracy of the predicted log β and pKa values (mean absolute deviations of 1.4 and 0.2 units respectively) is equivalent to the experimental uncertainties. This theoretical methodology provides direct knowledge of log β and pKa values of major and minor species, so it is of potential use in combination with experimental techniques to obtain a detailed description of the microscopic equilibria. In particular, the proposed methodology is shown to be especially useful for obtaining the real acidity constants of those chelates where the metal-ligand coordination changes as a result of ligand deprotonation. The stability and acidity constants of pyridoxamine-Cu(2+) chelates calculated with the proposed methodology show that pyridoxamine is an efficient scavenging agent of Cu(2+) under physiological pH conditions. This is of special interest as Cu(2+) overload is involved in the formation of advanced glycation end-products (AGEs) and their associated degenerative medical conditions.
“…Considering the 1 : 1 complexes in the higher protonation states (A-C), the B and C species are significantly more stable than chelate A. Additionally, and taking into account the experimental uncertainty in the log b values, the calculated stability values of B and C are in agreement with the reported experimental value. This reveals that PM acts as a monodentate ligand at low pH since the Cu 2+ competes against the protons for binding the amino and phenol groups, which supports the suppositions of El-Ezaby et al 68 The pK a values of the complexes calculated according to the reactions of eqn ( 9) and ( 12) (pK a (I) and pK a (II)) are reported in Table 3. In the case of complexes D, F and G, the pK a predictions show good agreement with the experimental values and allow the identification of the acidic groups with the pyridine nitrogen atoms.…”
Section: Stability Constants and Pk A Values Of Pm-cu Complexessupporting
confidence: 84%
“…The reported experimental log b values easily show differences of 0.5-1.5 log units, or even up to several log units in some extreme cases. 61,62,66,68 Therefore, the error in the log b value of the reference complex contributes significantly to the final error in the predicted stability constants. On the other hand, considering the magnitude of the experimental uncertainties, the log b values predicted with the proposed methodology match the precision of experiment.…”
Section: Theoretical Calculation Of Stability Constants Of Metal Comp...mentioning
Accurate prediction of thermodynamic constants of chemical reactions in solution is one of the current challenges in computational chemistry. We report a scheme for predicting stability constants (log β) and pKa values of metal complexes in solution by means of calculating free energies of ligand- and proton-exchange reactions using Density Functional Theory calculations in combination with a continuum solvent model. The accuracy of the predicted log β and pKa values (mean absolute deviations of 1.4 and 0.2 units respectively) is equivalent to the experimental uncertainties. This theoretical methodology provides direct knowledge of log β and pKa values of major and minor species, so it is of potential use in combination with experimental techniques to obtain a detailed description of the microscopic equilibria. In particular, the proposed methodology is shown to be especially useful for obtaining the real acidity constants of those chelates where the metal-ligand coordination changes as a result of ligand deprotonation. The stability and acidity constants of pyridoxamine-Cu(2+) chelates calculated with the proposed methodology show that pyridoxamine is an efficient scavenging agent of Cu(2+) under physiological pH conditions. This is of special interest as Cu(2+) overload is involved in the formation of advanced glycation end-products (AGEs) and their associated degenerative medical conditions.
“…Pyridoxamine (PM), a vitamin B 6 compound (Figure ), interacts with several metal ions in solution to form metal ion complexes of different stabilities. , 1 Structures of the ligands pyridoxamine (PM), glutamic acid (Glu), and aspartic acid (Asp).…”
Binary and ternary complexes involved in the systems pyridoxamine (PM), glutamic acid (Glu), or aspartic
acid (Asp) plus Ni(II) or Cu(II) were studied in solution at 0.15 M ionic strength and 25 °C by pH-metric,
absorpiometric, and polarographic techniques. The differential pulse polarographic technique was used
to study the reduction properties of these complexes. EPR was used to confirm the presence of binary
and ternary complex species in the Cu(II) systems. The stoichiometry and formation constants of the
binary and ternary complex species were determined by the SUPERQUAD program. Ternary species of
the types 1:1:1:r and 1:2:1:r (PM/Glu or Asp/M/H) were found to exist in the pH range ∼3 to ∼10.
“…The most stable Cu(II) complex with AMD is almost as stable as the most stable PM complex. The experimental formation constants ( ) of complexes {A9} and {A11} have been reported as 10.80 and 25.46 (from different groups), respectively [ 47 , 48 ]. These values were derived from the solvated ions in solutions of varying pH (ranging from 2.5 to 7.0).…”
The thermodynamic stability of 11 complexes of Cu(II) and 26 complexes of Fe(III) is studied, comprising the ligands pyridoxamine (PM), ascorbic acid (ASC), and a model Amadori compound (AMD). In addition, the secondary antioxidant activity of PM is analyzed when chelating both Cu(II) and Fe(III), relative to the rate constant of the first step of the Haber-Weiss cycle, in the presence of the superoxide radical anion (O2•−) or ascorbate (ASC−). Calculations are performed at the M05(SMD)/6-311+G(d,p) level of theory. The aqueous environment is modeled by making use of the SMD solvation method in all calculations. This level of theory accurately reproduces the experimental data available. When put in perspective with the stability of various complexes of aminoguanidine (AG) (which we have previously studied), the following stability trends can be found for the Cu(II) and Fe(III) complexes, respectively: ASC < AG < AMD < PM and AG < ASC < AMD < PM. The most stable complex of Cu(II) with PM (with two bidentate ligands) presents a ΔGf0 value of −35.8 kcal/mol, whereas the Fe(III) complex with the highest stability (with three bidentate ligands) possesses a ΔGf0 of −58.9 kcal/mol. These complexes can significantly reduce the rate constant of the first step of the Haber-Weiss cycle with both O2•− and ASC−. In the case of the copper-containing reaction, the rates are reduced up to 9.70 × 103 and 4.09 × 1013 times, respectively. With iron, the rates become 1.78 × 103 and 4.45 × 1015 times smaller, respectively. Thus, PM presents significant secondary antioxidant activity since it is able to inhibit the production of ·OH radicals. This work concludes a series of studies on secondary antioxidant activity and allows potentially new glycation inhibitors to be investigated and compared relative to both PM and AG.
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