Synthetic strategies for dinuclear platinum complexes containing inequivalent coordination spheres. Design of complexes capable of specific attack at one platinum center

Qu, Yun; Almeida, Sérgio Gama de; Farrell, Nicholas

doi:10.1016/s0020-1693(00)85322-0

Cited by 21 publications

(8 citation statements)

References 22 publications

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“…In a series of papers Farrell and coworkers [51][52][53][54][55][56][57][58] have used 195 Pt NMR to characterise various platinum amine complexes.…”

Section: Pt(ii) Complexesmentioning

confidence: 99%

“…12 A series of Pt-phosphine complexes with different olefin ligands. 42 their studies 56 the isomerisation of [(trans-PtCl 2 (Me 2 SO)) 2 -NH 2 (CH 2 ) 4 NH 2 ] to the dinuclear cis derivative was followed by 195 Pt NMR (see Fig. 16).…”

Section: Pt(ii) Complexesmentioning

confidence: 99%

“…Fig. 16 Isomerisation of the cis and trans complexes of [Pt{Cl 2 (Me 2 SO) 2 }m-NH 2 (CH 2 ) 4 NH 2 ] in DMSO-d 6 followed by195 Pt NMR 56. …”

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195Pt NMR—theory and application

et al. 2007

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This critical review highlights the progress in (195)Pt NMR over the last 25 years. In particular, some of the recent applications of (195)Pt NMR in catalytic and mechanistic studies, intermetallics and drug binding studies are discussed. (195)Pt NMR chemical shifts obtained from both theoretical studies and experiments are presented for Pt(0), Pt(II), Pt(III) and Pt(IV) complexes. (195)Pt coupling with various nuclei (viz. coupling constants) have also been collected in addition to data on (195)Pt relaxation. The latest developments in the theoretical knowledge and experimental advances have made (195)Pt NMR into a rich source of information in many fields. (164 references.).

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“…In a series of papers Farrell and coworkers [51][52][53][54][55][56][57][58] have used 195 Pt NMR to characterise various platinum amine complexes.…”

Section: Pt(ii) Complexesmentioning

confidence: 99%

Section: Pt(ii) Complexesmentioning

confidence: 99%

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195Pt NMR—theory and application

et al. 2007

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“…These new complexes contain just one leaving chloro group on each reactive platinum centre and have charges ranging from 1+ to 3+ [35][36][37][38][39][40][41][42][43]. The greatest potential for future anti-cancer agents, however, are those tri-and di-nuclear platinum complexes that contain just one chloro leaving group on each terminal platinum, trans to an aliphatic amine linking ligand that contains either a charged, inert central platinum centre or some other functional group that is capable of hydrogen bonding with DNA.…”

Section: Multi-nuclear Complexesmentioning

confidence: 99%

Multi-Nuclear Platinum Drugs: A New Paradigm in Chemotherapy

Wheate¹,

Jg²

2005

CMCACA

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The initial report of the therapeutic anticancer properties of a di-nuclear platinum complex in 1988 started a new paradigm in platinum based chemotherapy. Several multi-nuclear platinum complexes have entered clinical trials in recent years, with varying results. This group of charged complexes, consisting of di- and tri-nuclear compounds linked by aliphatic ligands, many with hydrogen bonding functionality, are able to overcome cisplatin and carboplatin resistance in many important human cancer cell lines. The adducts they form with DNA--which are, to some extent, affected by their pre-covalent association--are the reason for their increased cytotoxicity, and are distinctly different from those formed by cisplatin. Multi-nuclear platinum DNA adducts are broadly defined as flexible, non-directional and mainly interstrand cross-links. These complexes are also able to induce conformational changes in DNA, particularly the conversion from B-type to Z- and A-type. While these complexes are much more cytotoxic than cisplatin, they are also highly toxic. The maximum tolerated doses range from 0.006 to 1.1 mg/m(2) which is 10 to 100 fold lower than cisplatin. BBR3464 has shown in vivo activity at its MTD in several pre-clinical and clinical trials; however, recent phase II trials have shown that BBR3464, and other multi-nuclear platinum drugs, did not yield results substantially different from cisplatin, possibly due to their binding and degradation by human plasma proteins. This review will look at the success, and limitations, of multi-nuclear platinum drugs, and discuss their future potential as anti-cancer agents.

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“…0006-2960/93/0432-11794S04.00/0 © 1993 American Chemical Society Both antitumor activity and DNA binding activity vary with alterations of the backbone linker (chain length and steric effects), coordination sphere (one or two leaving groups), and coordination geometry (Farrell, 1993). In a model study, we have shown that dinuclear metal compounds with inequivalent coordination spheres may be designed that are capable of selective reaction at one coordination sphere (Qu et al, 1992).…”

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confidence: 99%

Homodinuclear (Pt,Pt) and heterodinuclear (Ru,Pt) metal compounds as DNA-protein cross-linking agents: Potential suicide DNA lesions

Houten¹,

Illenye²,

Qu³

et al. 1993

Biochemistry

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Homodinuclear (Pt,Pt) and heterodinuclear (Ru,Pt) metal compounds having the generalized formula M(a)NH2(CH)4NH2M(b) are shown to form specific DNA lesions which can efficiently cross-link proteins to DNA. In this study, the homodinuclear case is represented by M(a) = M(b) = [cis-Pt(Cl2)-(NH3)] and the heterodinuclear case is represented by M(a) = [cis-RuCl2(DMSO)3] and M(b) = [cis-PtCl2(NH3)]. Native and denaturing polyacrylamide gel electrophoresis was used to show the formation of ternary coordination complexes between the metal-treated 49-bp DNA fragment and the Escherichia coli UvrA and UvrB DNA repair proteins. Treatment with proteinase K results in loss of the DNA-protein cross-links. DNA-protein cross-links formed between UvrA and DNA previously modified with the dinuclear metal compounds are reversible with the reducing agent beta-mercaptoethanol. The DNA lesion responsible for efficient DNA-protein cross-linking is most probably a DNA-DNA interstrand cross-link in which each metal atom is coordinated with one strand of the DNA helix. The formation of DNA repair protein associated DNA cross-links, potential "suicide adducts", suggests a novel action mechanism for these anticancer compounds. In addition, these dinuclear metal compounds should be very useful agents for the investigation of a wide range of protein-DNA interactions.

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Synthetic strategies for dinuclear platinum complexes containing inequivalent coordination spheres. Design of complexes capable of specific attack at one platinum center

Cited by 21 publications

References 22 publications

195Pt NMR—theory and application

195Pt NMR—theory and application

Multi-Nuclear Platinum Drugs: A New Paradigm in Chemotherapy

Homodinuclear (Pt,Pt) and heterodinuclear (Ru,Pt) metal compounds as DNA-protein cross-linking agents: Potential suicide DNA lesions

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