PubMed Health⌕ Search

Biomedical subjects

P M May

Publications and source records attributed to P M May.

At least 19 recordsLinked to original sources
PubMed2001

Obtaining the 'best values' of stability constants: the protonation constants of five thioether carboxylates as a case study.

Computer speciation models often require large numbers of equilibrium constant values. For this purpose, state-of-the-art methods for experimental constant determination, best value constant selection from published values, and constant prediction based on quantitative structure-activity relationships, are evaluated through their application to the study of the protonation constants of five thioether carboxylates in aqueous solution at 37 degrees C and I = 150 mmol dm(-3) (NaCl).

Journal Article↗
PubMed2000

Complexation of iron(III) and iron(II) by citrate. Implications for iron speciation in blood plasma.

Estimates of the concentrations and identity of the predominant complexes of iron with the low-molecular-mass ligands in vivo are important to improve current understanding of the metabolism of this trace element. These estimates require a knowledge of the stability of the iron-citrate complexes. Previous studies on the equilibrium properties of the Fe(III)-citrate and Fe(II)-citrate are in disagreement. Accordingly, in this work, glass electrode potentiometric titrations have been used to re-determine the formation constants of both the Fe(III)- and Fe(II)-citrate systems at 25 degrees C in 1.00 M (Na)Cl and the reliability of these constants has been evaluated by comparing the measured and predicted redox potentials of the ternary Fe(III)-Fe(II)-citrate system. The formation constants obtained in this way were used in computer simulation models of the low-molecular-mass iron fraction in blood plasma. Redox equilibria of iron are thus included in large models of blood plasma for the first time. The results of these calculations show the predominance of Fe(II)-carbonate complexes and a significant amount of aquated Fe(II) in human blood plasma.

Citric Acid↗
PubMed1997

Complexation of copper(I) by thioamino acids. Implications for copper speciation in blood plasma.

There is mounting evidence that Cu(I) is the most important oxidation state of copper in many physiological systems. Research into Cu(I)-thioamino acid complex formation serves not only to improve the chelation therapy for treating copper intoxication but may also provide a better understanding of many facets of normal copper metabolism. Formation constants for the ternary mixed ligand complexes of Cu(I) with cysteine (Cys), glutathione (GSH) and penicillamine (Pen) are reported here for the first time. Potentiometric titrations, using techniques specially developed for the stabilization of aqueous Cu(I), were performed at 25 degrees C in 1.00 M (Na)Cl. It was found that precipitation severely limits the experimentally accessible pH range and, consequently, the computer analysis of the binary metal-ligand systems; however, it is also found that this is less of a problem when two different ligands are present. This latter fact permitted better models of the binary systems to be developed. The formation constants of Cu(I)-thioamino acids determined in this work were used in an improved computer simulation of copper speciation in blood plasma which, for the first time, incorporates redox equilibria.

Computer Simulation↗
PubMed1996

Biospeciation, by potentiometry and computer simulation, of Sm-EDTMP, a bone tumor palliative agent.

153Sm-EDTMP (ethylenediaminetetra(methylenephosphonic) acid) is of considerable interest as a bone therapeutic radiopharmaceutical but its properties in solution are not yet well characterized. The protonation constants of EDTMP and the formation constants of the complexes of Sm-EDTMP have accordingly been measured potentiometrically by glass electrode titrations at 25 degrees C in 0.15 M NaCl. Six protonation constants (log beta 011 = 9.638, log beta 012 = 17.330, log beta 013 = 23.597, 10g beta 014 = 28.636, log beta 015 = 31.501, log beta 016 = 32.624) and the formation constants of the [Sm(EDTMP)H-1]6-(log beta 11-1 = 4.865), [SmEDTMP]5-(log beta 110 = 12.018), [Sm(EDTMP)H]4- (log beta 111 = 17.892) and [Sm(EDTMP)H2]3- (log beta 112 = 23.437) complexes were determined. Computer simulations indicate that the [SmEDTMP]5- and the hydroxy [Sm(EDTMP)H-1]6- species are the major Sm(III) complexes formed in blood plasma, which explains the high degree of localization in the kidney and urine observed in biodistribution studies. Calcium ions are probably the major competitor for EDTMP in blood plasma. As the presence of secondary skeletal metastases results in a high rate of bone turnover, it is possible that the high concentration of calcium at these sites encourages localization of 153Sm-EDTMP.

Bone Neoplasms↗
PubMed1989

Iron chelators of the pyridoxal isonicotinoyl hydrazone class. III. Formation constants with calcium(II), magnesium(II) and zinc(II).

Formation constants for the calcium(II), magnesium(II) and zinc(II) complexes of the orally effective iron chelator, pyridoxal isonicotinoyl hydrazone (PIH) and three analogues, pyridoxal benzoyl hydrazone (PBH), pyridoxal p-methoxybenzoyl hydrazone (PpMBH) and pyridoxal m-fluorobenzoyl hydrazone (PmFBH) have been determined by potentiometry at 25 degrees C and I = 0.1 M [KNO3]. The four ligands bind calcium(II) weakly and magnesium(II) only slightly more strongly, as a 1:1 complex which is formed at pH greater than 8. The chelation of zinc(II) for all the ligands studied was greater than that for calcium(II) and magnesium(II), with complexation generally becoming significant at about pH 5. Thus, chelation of zinc(II) but not calcium(II) or magnesium(II) at physiological pH, 7.4 may be expected. Calculated values of the concentration of uncomplexed metal ion indicate that the selectivity of these ligands towards Fe(III) is comparable to that of the clinically used chelator desferrioxamine.

Calcium↗
PubMed1984

Metal binding by pharmaceuticals. Part 4. A comparative investigation of the interaction of metal ions with hydralazine, prizidilol and related compounds.

The metal complexing properties of two antihypertensive drugs, hydralazine (1-hydrazinophthalazine) and prizidilol (a hydrazinopyridazine), and some related ligands, have been studied using potentiometry, elemental analysis, spectrophotometry and computer simulation. The coordination chemistry of 1-hydrazinophthalazine and the hydrazinopyridazines is similar in that Ca(II), Mg(II), and Mn(II) complexes are not formed, whereas Zn(II), Cu(II) and Fe(II)/Fe(III) complexes are produced. Both kinds of ligand react with Fe(II) to form a brightly coloured tetrazene complex which is insoluble for hydralazine but soluble for prizidilol. Computer simulation studies indicate that the most prevalent metal complex of prizidilol in blood plasma is [Fe2+(Priz-)H+]2+ but that this only forms at very high drug concentrations. It is concluded that prizidilol is unlikely to have any direct effects on the metabolism or distribution of the trace elements listed here.

Chelating Agents↗
PubMed1984

Metal binding by pharmaceuticals. Part 5. Interaction of Cd(II), Ni(II) and Pb(II) with the intracellular hydrolysis products of the anti-tumour agent ICRF 159 and its inactive homologue ICRF 192.

Formation constants for the cadmium(II), nickel(II) and lead(II) complexes of DL-NN'-dicarboxamidomethyl-NN'-dicarboxymethyl-1,2-diaminopr opane (ICRF 198) and the 1,2-diaminobutane homologue (ICRF 226) have been measured potentiometrically at 37 degrees C and I = 150 mmol dm-3 [NaCl]. In all titrations a competing ligand, known to complex strongly with the metal ion, and having its formation constants predetermined, was employed. The constants are used in computer simulation models to assess the relative efficacy of the agents in mobilizing these metals from plasma proteins into low-molecular-weight complexes and the results are compared to those for known chelating agents. It is shown that the lead mobilizing potential of the agents is greater than either EDTA or D-penicillamine; they are, however, less adept in the removal of cadmium and nickel than other established agents.

Antineoplastic Agents↗
PubMed1984

Computer simulation of metal ion equilibria in biofluids. IV. Plutonium speciation in human blood plasma and chelation therapy using polyaminopolycarboxylic acids.

An investigation by computer simulation into the nature of Pu(IV) binding to low-molecular ligands in human blood plasma is described. Particular consideration is given to the interactions of various chelating agents which have been or might be used for treating plutonium intoxication. Formation constants of EDTA and DTPA with Cu(II), Mg(II), Mn(II), Zn(II), and Cd(II) have been measured under biologic conditions of temperature and background electrolyte. The relative ability of these and other chelating agents to cause excretion of plutonium and the concomitant loss of certain essential trace metals has thus been assessed.

Chelating Agents↗
PubMed1983

Metal binding by pharmaceuticals. Part 3. Copper (II) and zinc (II) interactions with isoniazid.

Formation constants for copper(II) and zinc(II) complexes of isonicotinoylhydrazine (isoniazid) and guanosine-5'-monophosphate have been measured potentiometrically at 37 degrees C, I = 150 mmol dm-3 [NaCl]. These constants have been used in computer models to assess the extent of complex formation by the drug in vivo. The simulations indicate that the predominant complexes existing in blood plasma are ternary species formed with histidinate. However, at clinical levels of isoniazid, it seems unlikely that these complexes are physiologically significant. On the other hand, ternary complex formation with nucleosides may be involved in the binding of isoniazid to viral RNA.

Copper↗
PubMed1982

Metal binding by pharmaceuticals. Part 2. Interactions of Ca(II), Cu(II), Fe(II), Mg(II), Mn(II) and Zn(II) with the intracellular hydrolysis products of the antitumour agent ICRF 159 and its inactive homologue ICRF 192.

Formation constants for the calcium(II), copper(II), iron(II), magnesium(II), manganese(II) and zinc(II) complexes of dl-NN'-dicarboxamidomethyl-NN'-dicarboxymethyl-1,2-diaminopropane (ICRF 198) and the 1,2-diamino-butane homologue (ICRF 226) have been measured potentiometrically at 37 degrees C and I=150 mmol dm-3 [NaCl]. The constants are used in computer simulation models to assess the relative avidity of these compounds for biologically essential metal ions in vivo. It is shown that the agents interact similarly with all of the ions studied except those of zinc(II), which are particularly strongly chelated by the hydrolysis product of ICRF 192. This effect could be responsible for the difference in cytotoxicity exhibited by the antitumour agent ICRF 159 (Razoxane) and its inactive homologue ICRF 192. However, the mechanism through which this might occur remains unclear.

Antineoplastic Agents↗
PubMed1981

Metal binding by pharmaceuticals. Part 1. Copper(II) and zinc(II) interactions following ethambutol administration.

Formation constants for copper(II) and zinc(II) complexes of dextro-2,2'-(ethylenediimino)-di-1-butanol (ethambutol) and its metabolic oxidation product, 2,2'-(ethylenediimino)-dibutyric acid (EDBA) have been measured potentiometrically at 37 degrees C, I = 0.15 mol dm-3 [NaCl]. The constants are used in computer models to assess the extent of the formation of these complexes in vivo. These simulations indicate that whereas ethambutol forms metal complexes only to a limited extent in vivo, EDBA competes effectively under physiological conditions for copper(II) and zinc(II). This study suggests that zinc(II) binding by EDBA may account for a number of side effects of ethambutol treatment.

Chelating Agents↗