Simultaneous determination of Pt and I by ICP-MS for studies of the mechanism of reaction of diiodoplatinum anticancer complexes

Abstract

The determination of Pt by ICP-MS in environmental and biological samples is well documented and generally performed after dissolution in dilute HNO 3.On the other hand, I is poorly ionised in the plasma and, at low pH, memory effects and instability arise from the formation of potentially volatile species, such as I 2 and HI, depending on the oxidation state of I. In order to investigate the role of iodo ligands in the design of Pt anticancer complexes, we have optimised conditions for the simultaneous determination of Pt and I. Standards and samples were diluted in 10 mM KOH and improved ion extraction into the quadrupole was achieved by means of an additional pump (S-Option@), leading to about a 2-fold increased sensitivity. The limits of detection in water were 10 and 0.6 ng l−1 for I and Pt, respectively, but increased to 23 ng l−1 for I and 2.2 ng l−1for Pt in KOH (10 mM ). The analysis of certified reference materials yielded the following results: 0.84±0.05 mg g−1 I (certified value: 0.81±0.05 mg g−1) in BCR CRM 063R 'Skimmed Milk Powder', and 0.121±0.006 mg ml−1 Pt (indicative value: 0.12 mg ml−1) in NIST SRM 2670 'Toxic Metals in Urine'. Pt5I ratios ranging from 0.240 to 1.035 were measured with an accuracy of 101.3±2.4%. The determination of the Pt5I ratio in the low M r fraction of reaction mixtures of diiodo Pt complexes and human albumin provided evidence for the release of iodide and for different kinetics for the reactions of diiodo Pt() and Pt() complexes.

Interactions of Antitumor Metallodrugs with Serum Proteins: Advances in Characterization Using Modern Analytical Methodology

“…Comparatively, studying the time course of the reaction of [Pt(en)I 2 ] 25 and the chloro-analogue 22 revealed that the diiodo complex reacts more rapidly with albumin but by the authors' observations gives no products with Pt coordinated to cysteine-34 . As another part of current work on the role of iodo ligands in the design of platinum anticancer complexes, the distribution of Pt and I among high and low M w fractions at different stages of the reaction of 24 and 25 with human albumin was investigated by ICP-MS. , The determination of the Pt/I ratio in the low M w fraction of reaction mixtures separated by ultrafiltration provided evidence for different kinetics for the albumin-binding reactions of diiodo Pt(II) and Pt(IV) complexes and for the release of iodide at an early stage of the reaction. Kratochwil and Bednarski explored a wider range of Pt(IV)−ethylenediamine complexes with the general formula [Pt(en)X 2 Y 2 ] (X = Cl; Y = Cl, OH, OCOCH 3 ; X = I; Y = Cl, OH, OCOCH 3 , OCOCF 3 , OSO 2 CH 3 ) with respect to the rate of their reduction by bovine serum albumin.…”

“…Regarding the determination of Pt in the presence of protein material, it should be noted that Sadler and co-workers were the first who demonstrated that ICP-MS with direct injection nebulization holds great promise to precisely measure Pt concentrations (down to 0.03 μg L -1 ) . Moreover, the capability of ICP-MS for multielement detection with an almost unrivaled sensitivity is of particular interest for investigations of the functions of transport proteins with affinity for more than one element (e.g., transferrin or metallothionein) and studies on the mechanism of action for newly designed drugs involving metal centers …”

“…142 Moreover, the capability of ICP-MS for multielement detection with an almost unrivaled sensitivity is of particular interest for investigations of the functions of transport proteins with affinity for more than one element (e.g., transferrin or metallothionein) and studies on the mechanism of action for newly designed drugs involving metal centers. 138 Recently developed tumor-inhibiting Pt(II) complexes with amino alcohol ligands capable of intramolecular ring formation, (SP-4-2)-bis(4-aminobutanol)dichloroplatinum(II) 29 and (SP-4-2)-bis[(R)-(-)-2-aminobutanol]dichloroplatinum-(II) 30 (Figure 16), were compared regarding their reactivity toward albumin using CE-ICP-MS. 38 It was demonstrated that interaction between the aminobutanol complexes and the protein, monitored over 6 days, shared a similar trend, adduct evolution being continued beyond a maximum evolution. A more thorough analysis of kinetic data revealed that 30 reacts with albumin slower than the corresponding 4-aminobutanol derivative 29 (k ) 2.5 × 10 -5 and 3.3 × 10 -5 s -1 , respectively).…”

Surprising Reactions of Iodo Pt(IV) and Pt(II) Complexes with Human Albumin: Detection of Cys34 Sulfenic Acid

“…A Plasma Quad 3 instrument (VG Elemental, Winsford, U.K.), equipped with the S-option for increased sensitivity, was used for all measurements. Details of the procedure used for the simultaneous determination of Pt and I on the high and low M r fractions by ICP-MS are reported elsewhere . Briefly, Pt complexes were incubated with either rHA or NEM-rHA at a molar ratio of 1:1 (100 μM) in 100 mM NaCl, 10 mM NaH 2 PO 4 , pH 7.4, at 310 K for 24 h. The binding of I - to albumin was assessed independently by incubating KI (200 μM) with rHA for 24 h in a 1:2 molar ratio.…”