Thermodynamic dissociation constants of risedronate using spectrophotometric and potentiometric pH-titration

Meloun, Milan; Ferenčíková, Zuzana; Málková, Hana; Pekárek, Tomáš

doi:10.2478/s11532-011-0150-3

Cited by 12 publications

(18 citation statements)

References 33 publications

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“…They coincide that the acid-base properties of risedronate in aqueous solution can be described in terms of four dissociation steps in a pH range from 2 to 12, the second step is related to the dissociation of the protonated nitrogen and the other steps are related to the dissociation of POH groups. The pKa values for the dissociation of the protonated nitrogen obtained, using different methodologies, are 5.66 [41], 5.7 [42], 5.9 [43], 6.29 [44] and 6.12 [44]. In all cases, this pKa is higher than that obtained for the pyridine (5.3).…”

Section: Ternary Complexes Of Hfppsmentioning

confidence: 41%

Mechanistic insights into protonation state as a critical factor in hFPPS enzyme inhibition

Ortega‐Castro

Marino

et al. 2015

J Comput Aided Mol Des

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Zoledronate and risedronate are the most powerful available nitrogen-containing bisphosphonates used in the treatment of bone-resorption disorders. Knowledge about inhibition mechanisms of these molecules is based on available crystallographic structures of human farnesyl pyrophosphate synthase (hFPPS). However, there is a lack of information explaining the inhibition potency of these two molecules compared to the natural substrate, dimethylallyl pyrophosphate. We carried out a molecular dynamics study that shown: (1) that NBPs potency is related to higher electrostatic interactions with the metallic cluster of the active site than to the natural substrate, and (2) the protonation of the R2 side chain is a critical factor to stabilize the NBPs into a closely irreversible ternary complex with the hFPPS.

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Section: Ternary Complexes Of Hfppsmentioning

confidence: 41%

Mechanistic insights into protonation state as a critical factor in hFPPS enzyme inhibition

Ortega‐Castro

Marino

et al. 2015

J Comput Aided Mol Des

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“…SQUAD is a program, created by David J. Leggett [13][14][15][16] that fits a set of absorption spectra corresponding to systems with variable chemical composition using a model (considering the formation constants of several chemical equilibria, the absorptivity coefficients for species and Beer's and additivity spectroscopic laws), by means of a Non Linear Least Squares algorithm. This program has been extensively used to determine equilibrium constants by UV-Visible measurements.…”

Section: Squadmentioning

confidence: 99%

“…Later, the pKa values for isomethiozin and methoprotryne, two triazine herbicides, are reported. In all cases, the pKa values were compared with those estimated through SQUAD [13,14], an algorithm that is widely used for this purpose [15,16].…”

Section: Introductionmentioning

confidence: 99%

New chemometric strategies in the spectrophotometric determination of pKa

et al. 2014

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KEYWORDSIn this work, principal component regression and partial least squares regression were used for the estimation of acid dissociation constants through UV-Vis spectrophotometric measurements, considering five well-known acid-base indicators as well as two herbicides as analytes. In each case, an acid-base titration was carried out. Then, the multivariate calibration model was constructed with a few absorption spectra of the series at extreme pH values, to which values of the dissociation fraction (α) of 1 or 0 were assigned, in the case of HA or A species. After that, the prediction step consisted in the estimation of α for the rest of the series. Then, distribution diagrams were built up with α vs pH, to find α = 0.5 where pH = pKa. The results were compared with those obtained through multivariate curve resolutionalternating least squares and program stability quotients from absorbance data (SQUAD), which showed an excellent correspondence. pKa PLS PCR MCR-ALS Spectrophotometry Chemometric strategies

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“…Potentiometric and spectrophotometric titrations are historically the standard methods for p K a measurements with the disadvantages of low sample throughput, large sample amount and limitations in sample impurities . p K a values have also been determined by analytical separation methods, first by isotachophoresis , followed by LC and CE with numerous advantages.…”

Section: Introductionmentioning

confidence: 99%

Estimation of acidity constants, ionic mobilities and charges of antimicrobial peptides by capillary electrophoresis

et al. 2016

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Capillary electrophoresis (CE) was employed for the determination of thermodynamic acidity constants (pK ) and actual ionic mobilities of polycationic antimicrobial peptides (AMPs). The effective electrophoretic mobilities of AMPs were measured by CE in a series of the background electrolytes within a wide pH range (2.00-12.25), at constant ionic strength (25 mM) and ambient temperature, using polybrene coated fused silica capillaries to suppress sorption of cationic AMPs to the capillary wall. Eventually, Haarhoff-Van der Linde peak fitting function was used for the determination of correct migration times of some AMPs peaks that were distorted by electromigration dispersion. The measured effective mobilities were corrected to 25°C. Mixed acidity constants, pKa,i mix , and actual ionic mobilities, m , of AMPs were determined by the nonlinear regression analysis of pH dependence of their effective mobilities. The pKa,i mix values were recalculated to thermodynamic pK s using the Debye-Hückel theory. Thermodynamic pK of imidazolium group of histidine residues was found to be in the range 3.72-4.98, pK of α-NH group was in the range 6.14-6.93, and pK of ε-NH group of lysine spanned the interval 7.26-9.84, depending on the particular amino acid sequence of the AMPs. Actual ionic mobilities of AMPs with positive charges from one to six elementary units achieved values (9.8 - 36.5) × 10 m V s .

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Thermodynamic dissociation constants of risedronate using spectrophotometric and potentiometric pH-titration

Abstract: Abstract:

Cited by 12 publications

References 33 publications

Mechanistic insights into protonation state as a critical factor in hFPPS enzyme inhibition

Mechanistic insights into protonation state as a critical factor in hFPPS enzyme inhibition

New chemometric strategies in the spectrophotometric determination of pKa

Estimation of acidity constants, ionic mobilities and charges of antimicrobial peptides by capillary electrophoresis

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