Calculation of equilibrium constants from multiwavelength spectroscopic data—IV Model-free least-squares refinement by use of evolving factor analysis

Gampp, Harald; Maeder, Marcel; Meyer, Charles J.; Zuberbühler, Andreas D.

doi:10.1016/0039-9140(86)80233-8

Cited by 496 publications

(284 citation statements)

References 19 publications

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“…The thermodynamic separation of the two single-electron transfers (the ∆E between the FAD ox /FAD sq and FAD sq / FAD red couples) was estimated from the maximal percentage of semiquinone formation during reduction in the absence of a dye (20) The extent of semiquinone formation was estimated both graphically by plotting the changes in absorbance at the maximum wavelength of the semiquinone (590 nm) versus that of the oxidized form (407 nm) and by "Eigenfactor" analysis of complete UV-vis spectra using Specfit32 (21).…”

Section: Determination Of the Redox Potentials Of Fad In Lppoxmentioning

confidence: 99%

Radical Phosphate Transfer Mechanism for the Thiamin Diphosphate- and FAD-Dependent Pyruvate Oxidase from Lactobacillus plantarum. Kinetic Coupling of Intercofactor Electron Transfer with Phosphate Transfer to Acetyl-thiamin Diphosphate via a Transient FAD Semiquinone/Hydroxyethyl-ThDP Radical Pair

et al. 2005

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The thiamin diphosphate (ThDP)-and flavin adenine dinucleotide (FAD)-dependent pyruvate oxidase from Lactobacillus plantarum catalyses the conversion of pyruvate, inorganic phosphate, and oxygen to acetyl-phosphate, carbon dioxide, and hydrogen peroxide. Central to the catalytic sequence, two reducing equivalents are transferred from the resonant carbanion/enamine forms of R-hydroxyethylThDP to the adjacent flavin cofactor over a distance of approximately 7 Å, followed by the phosphorolysis of the thereby formed acetyl-ThDP. Pre-steady-state and steady-state kinetics using time-resolved spectroscopy and a 1 H NMR-based intermediate analysis indicate that both processes are kinetically coupled. In the presence of phosphate, intercofactor electron-transfer (ET) proceeds with an apparent first-order rate constant of 78 s -1 and is kinetically gated by the preceding formation of the tetrahedral substrateThDP adduct 2-lactyl-ThDP and its decarboxylation. No transient flavin radicals are detectable in the reductive half-reaction. In contrast, when phosphate is absent, ET occurs in two discrete steps with apparent rate constants of 81 and 3 s -1 and transient formation of a flavin semiquinone/hydroxyethyl-ThDP radical pair. Temperature dependence analysis according to the Marcus theory identifies the second step, the slow radical decay to be a true ET reaction. The redox potentials of the FAD ox /FAD sq (E 1 ) -37 mV) and FAD sq /FAD red (E 2 ) -87 mV) redox couples in the absence and presence of phosphate are identical. Both the Marcus analysis and fluorescence resonance energy-transfer studies using the fluorescent N3′-pyridyl-ThDP indicate the same cofactor distance in the presence or absence of phosphate. We deduce that the exclusive 10 2 -10 3 -fold rate enhancement of the second ET step is rather due to the nucleophilic attack of phosphate on the kinetically stabilized hydroxyethyl-ThDP radical resulting in a low-potential anion radical adduct than phosphate in a docking site being part of a through-bonded ET pathway in a stepwise mechanism of ET and phosporolysis. Thus, LpPOX would constitute the first example of a radical-based phosphorolysis mechanism in biochemistry.Pyruvate oxidase from Lactobacillus plantarum (LpPOX, 1 EC 1.2.3.3) belongs to a superfamily of enzymes that utilize the cofactor thiamin diphosphate (ThDP), the biologically active derivative of vitamin B 1 . In addition to ThDP, LpPOX contains a flavin adenine dinucleotide (FAD) that is positioned at a distance of approximately 7 Å from the thiamin cofactor (Figure 1) (1).Pyruvate oxidase (POX) catalyses the conversion of pyruvate, inorganic phosphate, and oxygen to the high-energy metabolite acetyl phosphate, carbon dioxide, and hydrogen peroxide (2). Catalysis can be assumed to follow the typical Breslow mechanism of ThDP enzymes (Scheme 1). After ionization of the acidic C2-H of the thiazolium ring, pyruvate enters the active site where it reacts with the C2

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Section: Determination Of the Redox Potentials Of Fad In Lppoxmentioning

confidence: 99%

Radical Phosphate Transfer Mechanism for the Thiamin Diphosphate- and FAD-Dependent Pyruvate Oxidase from Lactobacillus plantarum. Kinetic Coupling of Intercofactor Electron Transfer with Phosphate Transfer to Acetyl-thiamin Diphosphate via a Transient FAD Semiquinone/Hydroxyethyl-ThDP Radical Pair

et al. 2005

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“…Computations relating to the determination of dissociation constants were performed by regression analysis of the UV/VIS spectra using the SPECFIT/32 [12][13][14][15][16] programmes. Most of graphs were plotted using ORIGIN 7.5 [49] and S-Plus [50].…”

Section: Computationsmentioning

confidence: 99%

“…However, a hard-modelling analysis cannot be applied if crucial information is missing. Softmodelling or model-free approaches, for example SPECFIT [12][13][14][15][16], are based on much more general prerequisites, such as positive molar absorbance, positive concentration of all species, unimodality of concentration profiles, and closure, that is, a concentration of all species is the same for all solutions. Naturally, if the strengths of hard-modelling and soft-modelling methodologies are combined, a much more powerful method of data analysis can be expected.…”

Section: Introductionmentioning

confidence: 99%

“…The aim of the study was to determine the pK T a values of clotrimazole, terbinafine HCl, acetylsalicylic acid, salicylic acid, and galanthamine using pH-spectrophotometric (15) titrations. The pK a values were also calculated theoretically using computer program (Pharma Algorithms) making predictions based on the structural formula of drug compounds.…”

Section: Introductionmentioning

confidence: 99%

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The Thermodynamic Dissociation Constants of Clotrimazole, Terbinafine HCL, Acetylsalicylic Acid, Salicylic Acid, and Galanthamine by the Nonlinear Regression of Multiwavelength Spectrophotometric pH-Titration Data

2010

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The mixed dissociation constants of five drugs-clotrimazole, terbinafine HCl, acetylsalicylic acid, salicylic acid, and galanthamineat various ionic strengths I and at temperatures of 25 • C and 37 • C were determined with the use of multiwavelength and multivariate treatments of spectral data SPECFIT/32 nonlinear regression analysis and INDICES factor analysis. The factor analysis in the INDICES program predicts the number of components, when the data quality is high and the instrumental error is known. The thermodynamic dissociation constant pK T a was estimated by nonlinear regression of {pK a, I} data at 25 • C and 37 • C: for clotrimazole pK T a,1 = 4.38(1) and 4.16(3); for terbinafine HCl pK T a,1 = 4.19(3) and 4.12(5); for acetylsalicylic acid pK T a,1 = 3.49(25) and 3.41(15); for salicylic acid pK T a,1 = 3.01(1) and 3.00(1) and for galanthamine pK T a,1 = 8.21(1) and 7.99(2) where in brackets the standard deviation is in the last significant digits. Goodness-of-fit tests for various regression diagnostics enabled the reliability of the parameter estimates found to be proven. Pharma Algorithms predicts pK a being based on the structural formulae of drug compounds.

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“…To initiate the iterative MCR-ALS procedure, an initial estimation is needed for the spectral profiles. Different methods are used for this purpose such as evolving factor analysis [32][33][34] , the determination of the purest variables [35][36][37][38] or by using pure spectra of the components 39 .…”

Section: Introductionmentioning

confidence: 99%

Characterization of sildenafil citrate tablets of different sources by near infrared chemical imaging and chemometric tools

Sabin

Lozano

Rocha

et al. 2013

Journal of Pharmaceutical and Biomedical Analysis

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In this paper the chemical imaging technique by near infrared spectroscopy was applied for characterization of drug formulations in tablets of sildenafil citrate of different sources. This work is original and has never been published because it was used the sildenafil citrate, including in the commercial one called "Viagra".In the first stage of the study, a chemometric method based on multivariate curve resolution was properly chosen for the development of the distribution map of concentrations of the active ingredient in tablets. In the second step, the normalized histograms of images from active ingredient were classified by hierarchical cluster analysis. Finally it was possible to recognize the patterns of homogeneity of images in sildenafil citrate tablet. This concept can be used to improve the knowledge of industrial products and processes, as well as, for characterization of counterfeit drugs.

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Calculation of equilibrium constants from multiwavelength spectroscopic data—IV Model-free least-squares refinement by use of evolving factor analysis

Cited by 496 publications

References 19 publications

Radical Phosphate Transfer Mechanism for the Thiamin Diphosphate- and FAD-Dependent Pyruvate Oxidase from Lactobacillus plantarum. Kinetic Coupling of Intercofactor Electron Transfer with Phosphate Transfer to Acetyl-thiamin Diphosphate via a Transient FAD Semiquinone/Hydroxyethyl-ThDP Radical Pair

Radical Phosphate Transfer Mechanism for the Thiamin Diphosphate- and FAD-Dependent Pyruvate Oxidase from Lactobacillus plantarum. Kinetic Coupling of Intercofactor Electron Transfer with Phosphate Transfer to Acetyl-thiamin Diphosphate via a Transient FAD Semiquinone/Hydroxyethyl-ThDP Radical Pair

The Thermodynamic Dissociation Constants of Clotrimazole, Terbinafine HCL, Acetylsalicylic Acid, Salicylic Acid, and Galanthamine by the Nonlinear Regression of Multiwavelength Spectrophotometric pH-Titration Data

Characterization of sildenafil citrate tablets of different sources by near infrared chemical imaging and chemometric tools

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