9 research outputs found
Protein Recognition of Gold-Based Drugs: 3D Structure of the Complex Formed When Lysozyme Reacts with Aubipy<sup>c</sup>
The
structure of the adduct formed in the reaction between Aubipy<sup>c</sup>, a cytotoxic organogoldÂ(III) compound, and the model protein
hen egg white lysozyme (HEWL) has been solved by X-ray crystallography.
It emerges that Aubipy<sup>c</sup>, after interaction with HEWL, undergoes
reduction of the goldÂ(III) center followed by detaching of the cyclometalated
ligand; the resulting naked goldÂ(I) ion is found bound to the protein
at Gln121. A direct comparison between the present structure and those
previously solved for the lysozyme adducts with other goldÂ(III) compounds
demonstrates that coordinated ligands play a key role in the protein–metallodrug
recognition process. Structural data support the view that goldÂ(III)-based
antitumor prodrugs are activated through metal reduction
Mesoionic Complexes of Platinum(II) Derived from “Rollover” Cyclometalation: A Delicate Balance between Pt–C(sp<sup>3</sup>) and Pt–C(sp<sup>2</sup>) Bond Cleavage as a Result of Different Reaction Conditions
“Rollover” cyclometalation is a particular
case of metal-mediated C–H bond activation, and the resulting
complexes constitute an emerging class of cyclometalated compounds.
In the case of 2,2′-bipyridine “rollover cyclometalation”
has been used to synthesize the complexes [PtÂ(bipy-H)Â(Me)Â(L)] (L =
PPh<sub>3</sub>, PCy<sub>3</sub>, PÂ(OPh)<sub>3</sub>, PÂ(<i>p</i>-tolyl)<sub>3</sub>), whose protonation produces a series of stable
corresponding pyridylenes [PtÂ(bipy*)Â(Me)Â(L)]<sup>+</sup>. The unusual
bipy* ligand may be described as an abnormal-remote heterocyclic chelated
carbene or simply as a mesoionic cyclometalated ligand. These cationic
species spontaneously convert in solution, through a retro-rollover
reaction, to the corresponding isomers [PtÂ(bipy)Â(Me)Â(L)]<sup>+</sup>, where the 2,2′-bipyridine is coordinated in the classical
N,N bidentate mode. Isomerization is achieved at different rates (ranging
over three orders of magnitude), depending on the nature of the phosphane
ligand, the most basic (PCy<sub>3</sub>) providing the fastest reaction.
The mesoionic species [PtÂ(bipy*)Â(Me)Â(L)]<sup>+</sup> contain two Pt–C
bonds: the balance between the Pt–CÂ(sp<sup>2</sup>) and Pt–CÂ(sp<sup>3</sup>) bond rupture is subtle, and competition is observed according
to the reaction conditions. In the presence of an external neutral
ligand L′ methane is released to give the cationic derivatives
[PtÂ(bipy-H)Â(L)Â(L′)]<sup>+</sup>, whereas reaction of the neutral
[PtÂ(bipy-H)Â(Me)Â(L)] with HCl may follow different routes depending
on the nature of the neutral ligand L. Assuming all reactions take
place through the formation of a hydride intermediate, quantum chemical
calculations show that computed energy barriers are qualitatively
consistent with observed reaction rates
Rollover Cyclometalation with 2‑(2′-Pyridyl)quinoline
Rollover
cyclometalation of 2-(2′-pyridyl)Âquinoline, L, allowed the
synthesis of the family of complexes [PtÂ(L-H)Â(X)Â(L′)] and [PtÂ(L*)Â(X)Â(L′)]Â[BF<sub>4</sub>] (X = Me, Cl; L′ = neutral ligand), the former being
the first examples of PtÂ(II) rollover complexes derived from the ligand
L. The ligand L* is a C,N cyclometalated, N-protonated isomer of L,
and can also be described as an abnormal-remote pyridylene. The corresponding
[PtÂ(L-H)Â(Me)Â(L′)]/[PtÂ(L*)Â(Me)Â(L′)]<sup>+</sup> complexes
constitute an uncommon Brønsted–Lowry acid–base
conjugated couple. The species obtained were investigated in depth
through NMR and UV–vis spectroscopy, cyclic voltammetry, and
density functional theory (DFT) methods to correlate different chemico-physical
properties with the nature of the cyclometalated ligand (e.g., L vs
bipy or L* vs L) and of the neutral ligand (DMSO, CO, PPh<sub>3</sub>). The crystal structures of [PtÂ(L-H)Â(Me)Â(PPh<sub>3</sub>)], [PtÂ(L-H)Â(Me)Â(CO)]
and [PtÂ(L*)Â(Me)Â(CO)]Â[BF<sub>4</sub>] were determined by X-ray powder
diffraction methods, the latter being the first structure of a PtÂ(II)-based,
protonated, rollover complex to be unraveled. The isomerization of
[PtÂ(L*)Â(Me)Â(PPh<sub>3</sub>)]<sup>+</sup> in solution proceeds through
a retro-rollover process to give the corresponding adduct [PtÂ(L)Â(Me)Â(PPh<sub>3</sub>)]<sup>+</sup>, where L acts as a classical N,N chelating
ligand. Notably, the retro-rollover reaction is the first process,
among the plethora of Pt–C bond protonolysis reactions reported
in the literature, where a Pt–CÂ(heteroaryl) bond is cleaved
rather than a Pt–CÂ(alkyl) one
Rollover Cyclometalation with 2‑(2′-Pyridyl)quinoline
Rollover
cyclometalation of 2-(2′-pyridyl)Âquinoline, L, allowed the
synthesis of the family of complexes [PtÂ(L-H)Â(X)Â(L′)] and [PtÂ(L*)Â(X)Â(L′)]Â[BF<sub>4</sub>] (X = Me, Cl; L′ = neutral ligand), the former being
the first examples of PtÂ(II) rollover complexes derived from the ligand
L. The ligand L* is a C,N cyclometalated, N-protonated isomer of L,
and can also be described as an abnormal-remote pyridylene. The corresponding
[PtÂ(L-H)Â(Me)Â(L′)]/[PtÂ(L*)Â(Me)Â(L′)]<sup>+</sup> complexes
constitute an uncommon Brønsted–Lowry acid–base
conjugated couple. The species obtained were investigated in depth
through NMR and UV–vis spectroscopy, cyclic voltammetry, and
density functional theory (DFT) methods to correlate different chemico-physical
properties with the nature of the cyclometalated ligand (e.g., L vs
bipy or L* vs L) and of the neutral ligand (DMSO, CO, PPh<sub>3</sub>). The crystal structures of [PtÂ(L-H)Â(Me)Â(PPh<sub>3</sub>)], [PtÂ(L-H)Â(Me)Â(CO)]
and [PtÂ(L*)Â(Me)Â(CO)]Â[BF<sub>4</sub>] were determined by X-ray powder
diffraction methods, the latter being the first structure of a PtÂ(II)-based,
protonated, rollover complex to be unraveled. The isomerization of
[PtÂ(L*)Â(Me)Â(PPh<sub>3</sub>)]<sup>+</sup> in solution proceeds through
a retro-rollover process to give the corresponding adduct [PtÂ(L)Â(Me)Â(PPh<sub>3</sub>)]<sup>+</sup>, where L acts as a classical N,N chelating
ligand. Notably, the retro-rollover reaction is the first process,
among the plethora of Pt–C bond protonolysis reactions reported
in the literature, where a Pt–CÂ(heteroaryl) bond is cleaved
rather than a Pt–CÂ(alkyl) one
Rollover Cyclometalation with 2‑(2′-Pyridyl)quinoline
Rollover
cyclometalation of 2-(2′-pyridyl)Âquinoline, L, allowed the
synthesis of the family of complexes [PtÂ(L-H)Â(X)Â(L′)] and [PtÂ(L*)Â(X)Â(L′)]Â[BF<sub>4</sub>] (X = Me, Cl; L′ = neutral ligand), the former being
the first examples of PtÂ(II) rollover complexes derived from the ligand
L. The ligand L* is a C,N cyclometalated, N-protonated isomer of L,
and can also be described as an abnormal-remote pyridylene. The corresponding
[PtÂ(L-H)Â(Me)Â(L′)]/[PtÂ(L*)Â(Me)Â(L′)]<sup>+</sup> complexes
constitute an uncommon Brønsted–Lowry acid–base
conjugated couple. The species obtained were investigated in depth
through NMR and UV–vis spectroscopy, cyclic voltammetry, and
density functional theory (DFT) methods to correlate different chemico-physical
properties with the nature of the cyclometalated ligand (e.g., L vs
bipy or L* vs L) and of the neutral ligand (DMSO, CO, PPh<sub>3</sub>). The crystal structures of [PtÂ(L-H)Â(Me)Â(PPh<sub>3</sub>)], [PtÂ(L-H)Â(Me)Â(CO)]
and [PtÂ(L*)Â(Me)Â(CO)]Â[BF<sub>4</sub>] were determined by X-ray powder
diffraction methods, the latter being the first structure of a PtÂ(II)-based,
protonated, rollover complex to be unraveled. The isomerization of
[PtÂ(L*)Â(Me)Â(PPh<sub>3</sub>)]<sup>+</sup> in solution proceeds through
a retro-rollover process to give the corresponding adduct [PtÂ(L)Â(Me)Â(PPh<sub>3</sub>)]<sup>+</sup>, where L acts as a classical N,N chelating
ligand. Notably, the retro-rollover reaction is the first process,
among the plethora of Pt–C bond protonolysis reactions reported
in the literature, where a Pt–CÂ(heteroaryl) bond is cleaved
rather than a Pt–CÂ(alkyl) one
Rollover Cyclometalation with 2‑(2′-Pyridyl)quinoline
Rollover
cyclometalation of 2-(2′-pyridyl)Âquinoline, L, allowed the
synthesis of the family of complexes [PtÂ(L-H)Â(X)Â(L′)] and [PtÂ(L*)Â(X)Â(L′)]Â[BF<sub>4</sub>] (X = Me, Cl; L′ = neutral ligand), the former being
the first examples of PtÂ(II) rollover complexes derived from the ligand
L. The ligand L* is a C,N cyclometalated, N-protonated isomer of L,
and can also be described as an abnormal-remote pyridylene. The corresponding
[PtÂ(L-H)Â(Me)Â(L′)]/[PtÂ(L*)Â(Me)Â(L′)]<sup>+</sup> complexes
constitute an uncommon Brønsted–Lowry acid–base
conjugated couple. The species obtained were investigated in depth
through NMR and UV–vis spectroscopy, cyclic voltammetry, and
density functional theory (DFT) methods to correlate different chemico-physical
properties with the nature of the cyclometalated ligand (e.g., L vs
bipy or L* vs L) and of the neutral ligand (DMSO, CO, PPh<sub>3</sub>). The crystal structures of [PtÂ(L-H)Â(Me)Â(PPh<sub>3</sub>)], [PtÂ(L-H)Â(Me)Â(CO)]
and [PtÂ(L*)Â(Me)Â(CO)]Â[BF<sub>4</sub>] were determined by X-ray powder
diffraction methods, the latter being the first structure of a PtÂ(II)-based,
protonated, rollover complex to be unraveled. The isomerization of
[PtÂ(L*)Â(Me)Â(PPh<sub>3</sub>)]<sup>+</sup> in solution proceeds through
a retro-rollover process to give the corresponding adduct [PtÂ(L)Â(Me)Â(PPh<sub>3</sub>)]<sup>+</sup>, where L acts as a classical N,N chelating
ligand. Notably, the retro-rollover reaction is the first process,
among the plethora of Pt–C bond protonolysis reactions reported
in the literature, where a Pt–CÂ(heteroaryl) bond is cleaved
rather than a Pt–CÂ(alkyl) one
Structure–Activity Relationships in Cytotoxic Au<sup>I</sup>/Au<sup>III</sup> Complexes Derived from 2‑(2′-Pyridyl)benzimidazole
GoldÂ(I)
and goldÂ(III) complexes derived from 2-(2′-pyridyl)Âbenzimidazole
(pbiH) were proven to be a promising class of in vitro antitumor agents
against A2780 human ovarian cancer cells. In this paper, a comparative
electrochemical, UV–vis absorption, and emission spectroscopic
investigation is reported on pbiH, the two mononuclear Au<sup>III</sup> complexes [(pbi)ÂAuX<sub>2</sub>] (X = Cl (<b>1</b>), AcO (<b>2</b>)), the four mononuclear Au<sup>I</sup> derivatives [(pbiH)ÂAuCl]
(<b>3</b>), [(pbiH)ÂAuÂ(PPh<sub>3</sub>)]ÂPF<sub>6</sub> ((<b>4</b><sup>+</sup>)Â(PF<sub>6</sub><sup>–</sup>)), [(pbi)ÂAuÂ(PPh<sub>3</sub>)] (<b>5</b>), and [(pbi)ÂAuÂ(TPA)] (<b>6</b>),
the three mixed-valence Au<sup>III</sup>/Au<sup>I</sup> complexes
[(ÎĽ-pbi)ÂAu<sub>2</sub>Cl<sub>3</sub>] (<b>7</b>), [(Ph<sub>3</sub>P)ÂAuÂ(ÎĽ-pbi)ÂAuX<sub>2</sub>]ÂPF<sub>6</sub> (X = Cl ((<b>8</b><sup>+</sup>)Â(PF<sub>6</sub><sup>–</sup>)), AcO ((<b>9</b><sup>+</sup>)Â(PF<sub>6</sub><sup>–</sup>))), and the
binuclear Au<sup>I</sup>–Au<sup>I</sup> compound [(ÎĽ-pbi)ÂAu<sub>2</sub>(PPh<sub>3</sub>)<sub>2</sub>]ÂPF<sub>6</sub> ((<b>10</b><sup>+</sup>)Â(PF<sub>6</sub><sup>–</sup>)). All complexes
feature irreversible reduction processes related to the Au<sup>III</sup>/Au<sup>I</sup> or Au<sup>I</sup>/Au<sup>0</sup> processes and peculiar
luminescent emission at about 360–370 nm in CH<sub>2</sub>Cl<sub>2</sub>, with quantum yields that are remarkably lower ((0.7–14.5)
× 10<sup>–2</sup>) in comparison to that determined for
the free pbiH ligand (31.5 × 10<sup>–2</sup>) in the same
solvent. The spectroscopic and electrochemical properties of all complexes
were interpreted on the grounds of time-dependent PBE0/DFT calculations
carried out both in the gas phase and in CH<sub>2</sub>Cl<sub>2</sub> implicitly considered within the IEF-PCM SCRF approach. The electronic
structure of the complexes, and in particular the energy and composition
of the Kohn–Sham LUMOs, can be related to the antiproliferative
properties against the A2780 ovarian carcinoma cell line, providing
sound quantitative structure–activity relationships and shedding
a light on the role played by the global charge and nature of ancillary
ligands in the effectiveness of Au-based antitumor drugs
Heterobimetallic Rollover Derivatives
Heterobimetallic complexes with metal centers connected
by a small
delocalized ligand constitute an interesting class of compounds. Here
we report that starting from the mononuclear platinumÂ(II) rollover
complexes [PtÂ(bipy-H)Â(L)ÂCl] (bipy-H = 2,2′-bipyridine C(3′)-N
cyclometalated, L= DMSO, PPh<sub>3</sub>) a second rollover cyclometalation
may produce a series of PtÂ(II)/PdÂ(II) heterobimetallic complexes where
the two metals are linked by the planar, highly delocalized, doubly
deprotonated 2,2′-bipyridine
Heterobimetallic Rollover Derivatives
Heterobimetallic complexes with metal centers connected
by a small
delocalized ligand constitute an interesting class of compounds. Here
we report that starting from the mononuclear platinumÂ(II) rollover
complexes [PtÂ(bipy-H)Â(L)ÂCl] (bipy-H = 2,2′-bipyridine C(3′)-N
cyclometalated, L= DMSO, PPh<sub>3</sub>) a second rollover cyclometalation
may produce a series of PtÂ(II)/PdÂ(II) heterobimetallic complexes where
the two metals are linked by the planar, highly delocalized, doubly
deprotonated 2,2′-bipyridine