Robust Structure and Reactivity of Aqueous Arsenous Acid–Platinum(II) Anticancer Complexes

Abstract

The first molecular adducts of platinum and arsenic based anticancer drugs - arsenoplatins - show unanticipated structure, substitution chemistry, and cellular cytotoxicity. The PtII-AsIII bonds in these complexes are stable in aqueous solution and strongly influence the lability of the trans ligand.

Anticancer Activity of Small-Molecule and Nanoparticulate Arsenic(III) Complexes

“…In arsenoplatin-1 (1) (Figure 9) platinum forms expected square planar geometry, but arsenic(III) forms trigonal bipyramidal geometry with arsenic(III) acting unexpectedly as a Lewis base and as a Lewis acid simultaneously. 135 Multiple interactions of arsenic(III) are partly responsible for the very short Pt II -As III bonds in these complexes which are in 2.2687(4)- 2.2732 (3) Å range. The shortest bond obtained is just 0.0012 Å longer than the shortest Pt II -As III bond found in one organoarsenical compound according the CSD.…”

“…135 The new complexes were synthesized from cisplatin and arsenic trioxide in water-nitrile mixture. In arsenoplatin-1 (1) (Figure 9) platinum forms expected square planar geometry, but arsenic(III) forms trigonal bipyramidal geometry with arsenic(III) acting unexpectedly as a Lewis base and as a Lewis acid simultaneously.…”

“…Substitution of chloride ion in arsenoplatin-1 with thiocyanate ion in water occurs immediately at room temperature, and the addition of AgNO 3 to facilitate substitution is not necessary (Scheme 1). 135 …”

Trans–cis isomerization of [(C6H5)3P]2PtCl2 complex in dimethylformamide solutions

“…Since the Cl À ion has a larger trans effect than the NH 3 molecule, the second ammine ligand preferentially substitutes trans to the chloride ligand, and therefore cis to the first ammine molecule. The trans effect of the halides follows the order I À > Br À > Cl À , therefore the synthesis is conducted using [PtI 4 ] 2À to ensure a high yield and purity of the cis isomer, followed by the conversion of PtI 2 (NH 3 ) 2 into PtCl 2 (NH 3 ) 2 [2]. Structure-activity relationships for a class of platinum coordination compounds confirm that only these with the cis geometry block a cell growth.…”

Triphenylarsonium-functionalised gold nanoparticles: potential nanocarriers for intracellular therapeutics

“…2 Historically, arsenic compounds have been widely investigated for their medicinal properties although interest declined as greater understanding of their toxicity became apparent. 1,5 More recently there has been a resurgence of interest in the medicinal properties of arsenic compounds, including the use of arsenic trioxide and organic arsenic derivatives as treatments for leukaemia and other cancers, 1,3,4 the characterisation of an arsenic trioxide analogue of cisplatin, 6 and the observation that 72 As and 74 As radiopharmaceuticals could be useful in positron emission tomography (PET). 1,5 More recently there has been a resurgence of interest in the medicinal properties of arsenic compounds, including the use of arsenic trioxide and organic arsenic derivatives as treatments for leukaemia and other cancers, 1,3,4 the characterisation of an arsenic trioxide analogue of cisplatin, 6 and the observation that 72 As and 74 As radiopharmaceuticals could be useful in positron emission tomography (PET).…”