Mono- and bimetallic homo- and heterodinuclear Pd and Pt complexes bridged by diphosphines: synthesis, characterisation and cytotoxicity

Basile Roufosse; Tomas Brice; Marco Papaldo; Lucy W. Macharia; Karabo Serala; Mihlali V. Mlaza; Thato T. Medupe; Sharon Prince; Christoph Marschner; Thomas J. Cleij; Burgert Blom

doi:10.1039/d5dt02044a

Mono- and bimetallic homo- and heterodinuclear Pd and Pt complexes bridged by diphosphines: synthesis, characterisation and cytotoxicity

Basile Roufosse
, Tomas Brice
, Marco Papaldo
, Lucy W. Macharia
, Karabo Serala
, Mihlali V. Mlaza
, Thato T. Medupe
, Sharon Prince^*
, Christoph Marschner
, Thomas J. Cleij
, Burgert Blom^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Herein we report a series of monometallic complexes: [(κ ²-dppe)MCl(κ ¹-dppx)](OTf) (where dppe = 1,2-bis(diphenylphosphino)ethane; dppx = 1,4-bis(diphenylphosphino)butane (dppb) (M = Pd (Pd-1) or Pt (Pt-1)), 1,5-bis(diphenylphosphino)pentane (dpppent) (M = Pd (Pd-2) or Pt (Pt-2)), or 1,6-bis(diphenylphosphino)hexane (dpph) (M = Pd (Pd-3) or Pt (Pt-3))). We also report the homobimetallic complexes [((κ ²-dppe)PdCl) ₂(μ-dppx)](2OTf) (dppx = dppb (PdPd-1), dpppent (PdPd-2) or dpph (PdPd-3)). In addition, the Ru(ii)-based heterobimetallic complexes [(κ ²-dppe)ClM(μ-dppx)RuCl ₂(η ⁶-p-cym)](OTf) (M = Pd and dppx = dppb (PdRu-1), M = Pd and dppx = dpppent (PdRu-2), M = Pd and dppx = dpph (PdRu-3), M = Pt and dppx = dppb (PtRu-1), M = Pt and dppx = dpppent (PtRu-2), M = Pt and dppx = dpph (PtRu-3), and Os-based heterobimetallic complexes [(κ ²-dppe)ClPd(μ-dppx)OsCl ₂(η ⁶-p-cym)](OTf) (dppx = dppb (PdOs-1), dpppent (PdOs-2) and dpph (PdOs-3)) are also reported. All complexes were fully characterised by spectroscopic means and their stability in DMSO was determined via time-dependent NMR spectroscopy. Aquation studies were performed in a PBS buffer : DMSO solution (90 : 10 v/v) at 37 °C to determine the various entities which could form in biological media and are discussed. The solid-state structures of complexes PdPd-0, PdPd-1 and PdRu-1 were further characterised by single crystal X-ray diffraction analyses and are reported. The cytotoxicity of all complexes was evaluated in vitro against a wide panel of cancer cell lines. While the monometallic and homobimetallic complexes showed sub-optimal activity, the heterobimetallic complexes all displayed good to excellent cytotoxicity. PdRu-1 displayed an IC ₅₀ value of 3.43 ± 1.43 µM and a selectivity index of 6.16 on the Ca Ski cell line. The results from this study highlight the increased efficacy of heterobimetallic systems with regards to their monometallic or homobimetallic counterparts for Pd(ii) and Pt(ii) type complexes.

Original language	English
Pages (from-to)	865-884
Number of pages	20
Journal	Dalton Transactions
Volume	55
Issue number	2
DOIs	https://doi.org/10.1039/d5dt02044a
Publication status	Published - 13 Jan 2026

Keywords

HARD LIGANDS
SOFT METALS
ANTIPROLIFERATIVE ACTIVITY
IN-VITRO
PALLADIUM(II)
PLATINUM(II)
RUTHENIUM(II)
PHOSPHINE
DONORS
PH

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@article{ecd5e1281b714e2b98e75270092de53f,

title = "Mono- and bimetallic homo- and heterodinuclear Pd and Pt complexes bridged by diphosphines: synthesis, characterisation and cytotoxicity",

abstract = "Herein we report a series of monometallic complexes: [(κ 2-dppe)MCl(κ 1-dppx)](OTf) (where dppe = 1,2-bis(diphenylphosphino)ethane; dppx = 1,4-bis(diphenylphosphino)butane (dppb) (M = Pd (Pd-1) or Pt (Pt-1)), 1,5-bis(diphenylphosphino)pentane (dpppent) (M = Pd (Pd-2) or Pt (Pt-2)), or 1,6-bis(diphenylphosphino)hexane (dpph) (M = Pd (Pd-3) or Pt (Pt-3))). We also report the homobimetallic complexes [((κ 2-dppe)PdCl) 2(μ-dppx)](2OTf) (dppx = dppb (PdPd-1), dpppent (PdPd-2) or dpph (PdPd-3)). In addition, the Ru(ii)-based heterobimetallic complexes [(κ 2-dppe)ClM(μ-dppx)RuCl 2(η 6-p-cym)](OTf) (M = Pd and dppx = dppb (PdRu-1), M = Pd and dppx = dpppent (PdRu-2), M = Pd and dppx = dpph (PdRu-3), M = Pt and dppx = dppb (PtRu-1), M = Pt and dppx = dpppent (PtRu-2), M = Pt and dppx = dpph (PtRu-3), and Os-based heterobimetallic complexes [(κ 2-dppe)ClPd(μ-dppx)OsCl 2(η 6-p-cym)](OTf) (dppx = dppb (PdOs-1), dpppent (PdOs-2) and dpph (PdOs-3)) are also reported. All complexes were fully characterised by spectroscopic means and their stability in DMSO was determined via time-dependent NMR spectroscopy. Aquation studies were performed in a PBS buffer : DMSO solution (90 : 10 v/v) at 37 °C to determine the various entities which could form in biological media and are discussed. The solid-state structures of complexes PdPd-0, PdPd-1 and PdRu-1 were further characterised by single crystal X-ray diffraction analyses and are reported. The cytotoxicity of all complexes was evaluated in vitro against a wide panel of cancer cell lines. While the monometallic and homobimetallic complexes showed sub-optimal activity, the heterobimetallic complexes all displayed good to excellent cytotoxicity. PdRu-1 displayed an IC 50 value of 3.43 ± 1.43 µM and a selectivity index of 6.16 on the Ca Ski cell line. The results from this study highlight the increased efficacy of heterobimetallic systems with regards to their monometallic or homobimetallic counterparts for Pd(ii) and Pt(ii) type complexes.",

keywords = "HARD LIGANDS, SOFT METALS, ANTIPROLIFERATIVE ACTIVITY, IN-VITRO, PALLADIUM(II), PLATINUM(II), RUTHENIUM(II), PHOSPHINE, DONORS, PH",

author = "Basile Roufosse and Tomas Brice and Marco Papaldo and Macharia, \{Lucy W.\} and Karabo Serala and Mlaza, \{Mihlali V.\} and Medupe, \{Thato T.\} and Sharon Prince and Christoph Marschner and Cleij, \{Thomas J.\} and Burgert Blom",

year = "2026",

month = jan,

day = "13",

doi = "10.1039/d5dt02044a",

language = "English",

volume = "55",

pages = "865--884",

journal = "Dalton Transactions",

issn = "1477-9226",

publisher = "Royal Society of Chemistry",

number = "2",

}

TY - JOUR

T1 - Mono- and bimetallic homo- and heterodinuclear Pd and Pt complexes bridged by diphosphines

T2 - synthesis, characterisation and cytotoxicity

AU - Roufosse, Basile

AU - Brice, Tomas

AU - Papaldo, Marco

AU - Macharia, Lucy W.

AU - Serala, Karabo

AU - Mlaza, Mihlali V.

AU - Medupe, Thato T.

AU - Prince, Sharon

AU - Marschner, Christoph

AU - Cleij, Thomas J.

AU - Blom, Burgert

PY - 2026/1/13

Y1 - 2026/1/13

N2 - Herein we report a series of monometallic complexes: [(κ 2-dppe)MCl(κ 1-dppx)](OTf) (where dppe = 1,2-bis(diphenylphosphino)ethane; dppx = 1,4-bis(diphenylphosphino)butane (dppb) (M = Pd (Pd-1) or Pt (Pt-1)), 1,5-bis(diphenylphosphino)pentane (dpppent) (M = Pd (Pd-2) or Pt (Pt-2)), or 1,6-bis(diphenylphosphino)hexane (dpph) (M = Pd (Pd-3) or Pt (Pt-3))). We also report the homobimetallic complexes [((κ 2-dppe)PdCl) 2(μ-dppx)](2OTf) (dppx = dppb (PdPd-1), dpppent (PdPd-2) or dpph (PdPd-3)). In addition, the Ru(ii)-based heterobimetallic complexes [(κ 2-dppe)ClM(μ-dppx)RuCl 2(η 6-p-cym)](OTf) (M = Pd and dppx = dppb (PdRu-1), M = Pd and dppx = dpppent (PdRu-2), M = Pd and dppx = dpph (PdRu-3), M = Pt and dppx = dppb (PtRu-1), M = Pt and dppx = dpppent (PtRu-2), M = Pt and dppx = dpph (PtRu-3), and Os-based heterobimetallic complexes [(κ 2-dppe)ClPd(μ-dppx)OsCl 2(η 6-p-cym)](OTf) (dppx = dppb (PdOs-1), dpppent (PdOs-2) and dpph (PdOs-3)) are also reported. All complexes were fully characterised by spectroscopic means and their stability in DMSO was determined via time-dependent NMR spectroscopy. Aquation studies were performed in a PBS buffer : DMSO solution (90 : 10 v/v) at 37 °C to determine the various entities which could form in biological media and are discussed. The solid-state structures of complexes PdPd-0, PdPd-1 and PdRu-1 were further characterised by single crystal X-ray diffraction analyses and are reported. The cytotoxicity of all complexes was evaluated in vitro against a wide panel of cancer cell lines. While the monometallic and homobimetallic complexes showed sub-optimal activity, the heterobimetallic complexes all displayed good to excellent cytotoxicity. PdRu-1 displayed an IC 50 value of 3.43 ± 1.43 µM and a selectivity index of 6.16 on the Ca Ski cell line. The results from this study highlight the increased efficacy of heterobimetallic systems with regards to their monometallic or homobimetallic counterparts for Pd(ii) and Pt(ii) type complexes.

AB - Herein we report a series of monometallic complexes: [(κ 2-dppe)MCl(κ 1-dppx)](OTf) (where dppe = 1,2-bis(diphenylphosphino)ethane; dppx = 1,4-bis(diphenylphosphino)butane (dppb) (M = Pd (Pd-1) or Pt (Pt-1)), 1,5-bis(diphenylphosphino)pentane (dpppent) (M = Pd (Pd-2) or Pt (Pt-2)), or 1,6-bis(diphenylphosphino)hexane (dpph) (M = Pd (Pd-3) or Pt (Pt-3))). We also report the homobimetallic complexes [((κ 2-dppe)PdCl) 2(μ-dppx)](2OTf) (dppx = dppb (PdPd-1), dpppent (PdPd-2) or dpph (PdPd-3)). In addition, the Ru(ii)-based heterobimetallic complexes [(κ 2-dppe)ClM(μ-dppx)RuCl 2(η 6-p-cym)](OTf) (M = Pd and dppx = dppb (PdRu-1), M = Pd and dppx = dpppent (PdRu-2), M = Pd and dppx = dpph (PdRu-3), M = Pt and dppx = dppb (PtRu-1), M = Pt and dppx = dpppent (PtRu-2), M = Pt and dppx = dpph (PtRu-3), and Os-based heterobimetallic complexes [(κ 2-dppe)ClPd(μ-dppx)OsCl 2(η 6-p-cym)](OTf) (dppx = dppb (PdOs-1), dpppent (PdOs-2) and dpph (PdOs-3)) are also reported. All complexes were fully characterised by spectroscopic means and their stability in DMSO was determined via time-dependent NMR spectroscopy. Aquation studies were performed in a PBS buffer : DMSO solution (90 : 10 v/v) at 37 °C to determine the various entities which could form in biological media and are discussed. The solid-state structures of complexes PdPd-0, PdPd-1 and PdRu-1 were further characterised by single crystal X-ray diffraction analyses and are reported. The cytotoxicity of all complexes was evaluated in vitro against a wide panel of cancer cell lines. While the monometallic and homobimetallic complexes showed sub-optimal activity, the heterobimetallic complexes all displayed good to excellent cytotoxicity. PdRu-1 displayed an IC 50 value of 3.43 ± 1.43 µM and a selectivity index of 6.16 on the Ca Ski cell line. The results from this study highlight the increased efficacy of heterobimetallic systems with regards to their monometallic or homobimetallic counterparts for Pd(ii) and Pt(ii) type complexes.

KW - HARD LIGANDS

KW - SOFT METALS

KW - ANTIPROLIFERATIVE ACTIVITY

KW - IN-VITRO

KW - PALLADIUM(II)

KW - PLATINUM(II)

KW - RUTHENIUM(II)

KW - PHOSPHINE

KW - DONORS

KW - PH

U2 - 10.1039/d5dt02044a

DO - 10.1039/d5dt02044a

M3 - Article

SN - 1477-9226

VL - 55

SP - 865

EP - 884

JO - Dalton Transactions

JF - Dalton Transactions

IS - 2

ER -

Mono- and bimetallic homo- and heterodinuclear Pd and Pt complexes bridged by diphosphines: synthesis, characterisation and cytotoxicity

Abstract

Keywords

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