Penicillamine complexes

Penicillamine is known to form complexes of varying stability with several metal ions. In neutral solution, penicillamine complexes with mercury, lead, nickel, and copper are relatively more stable than those of zinc, iron, and manganese. The three functional groups of penicillamine may be engaged in the formation of metal complex, and the resultant compounds may be polymeric in structure. 

Solution equilibria of Fe(III)/Cr(III) in methionine and Fe(III)/Cr(III) in methio-nine/penicillamine complex systems were studied by paper electrophoresis and were reported by Tewari [38]. The formation of 1 1 1 mixed ligand complexes is inferred, and the stability constants of the complexes at 35 °C and 0.1 M ionic strength were 6.80 0.09 (Fe(III) methionine penicillamine) and 4.60 0.16 (Cr(III)-methionine-penicillamine), respectively. 

An ionophoretic method was described by Tewari [41] for the study of equilibria in a mixed ligand complex system in solution. This method is based on the movement of a spot of metal ion in an electric field with the complexants added in the background electrolyte at pH 8.5. The concentration of the primary ligand (nitrilo-triacetate) was kept constant, while that of the secondary ligand (penicillamine) was varied. The stability constants of the metal nitrilotriacetate-penicillamine complexes have been found to be 6.26 0.09 and 6.68 0.13 (log K values) for the Al(III) and Th(IV) complexes, respectively, at 35 °C and an ionic strength of 0.1 M. 

However, a second agent shown in the PMI curves is that of D-peni-cillamine. Upon studying the speciation of that agent in blood plasma it is found that this is electrically net-neutral and therefore is able to penetrate into tissue. Further, the PMI curves indicate that it is able to complex with lead ions and to form a net-neutral lead-penicillaminate complex. This then passes out of the cell membrane into the blood plasma where it remains net-neutral and thus is not amenable to kidney excretion. 

Yokoyama A, Horiuchi K, Hata N et al (1979) Technetium in technetium-99m radiopharmaceuticals. I. Tetravalent mononuclear technetium penicillamine complex. J Labeled Compd Radio-pharm 16 80-81... 

Only dose of this penicillamine complex tested. 

Patents have issued for the use of amino-acid complexes [253], copper-metallothioneins [254], compositions of copper compounds mixed with fatty acids [253], copper complexes of D-penicillamine, alkylcysteines [256, 257] and copper complexes offatty acids alone or mixed with metallic copper [258]. Compositions of copper compounds mixed with fatty acids were also claimed to be useful in the treatment of other inflammatory disorders, including cardiovascular and thrombotic disorders, menstrual cycle disorders, diabetes, endometriosis, nutritional deficiencies and malignancies [255]. Scheinberg has also obtained a Food and Drug Administration approved Investigational New Drug application for the treatment of RA with the mixed-valence copper penicillamine complex (personal communication). Preparations of Cu(II)-(oleate) are currently being sold in Europe for topical treatment of RA and other inflammatory disorders under the trade names of Kupfer and Kupfer Forte, which contains fine particles of metallic copper [258]. 

A subsequent comparison of the relative antiulcer activities of three different penicillamine complexes in the Shay ulcer model revealed that the water-soluble mixed-valence complex, NasCu(I)gCu(II)6(Penicillamine)i2Cl, was... 

Studies of the interaction of administered copper (5 mg/day) and penicillamine (500 mg/day) have provided evidence that the penicillamine complex... 

Another example demonstrating that technetium compounds are more reactive than the analogous compounds of rhenium is the racemization of the penicillamine complexes of Tc(V) and Re(V). The complexes are six-coordinate in solution with one tridentate and one bidentatc penicillamine (pen) and one oxo ligand. Both mixed ligand anionic complexes l(/9-pcn)(L-pcn)TcO] and [(D-pcn)(T-pen)ReO]" undergo a unimolecular racemization by exchange of carboxylates at the site trans to the oxo ligand ... 

D-Penicillamine 11.26), similarly used in copper poisoning, is non-toxic. It is employed in Wilson s disease, an inherited error of metabolism in which dietary copper cannot be eliminated, but accumulates in brain, kidneys, and liver in such quantities that death occurs in the early years of life. Oral administration of penicillamine prevents this and can even reverse the pathological lesions produced by the copper ions. The copper—penicillamine complex is readily voided in the urine (Walshe, 1968). Penicillamine, being effective orally, is convenient to use in the later stages of treating chronic lead poisoning with intravenous EDTA. 

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