Nickel-bis(dithiolene) containing NPs: controlled release of Dox and photothermal therapy under N... more Nickel-bis(dithiolene) containing NPs: controlled release of Dox and photothermal therapy under NIR Irradiation.
The use of an interleukin β antibody is currently being investigated in the clinic for the treatm... more The use of an interleukin β antibody is currently being investigated in the clinic for the treatment of acne, a dermatological disorder affecting 650M persons globally. Inhibiting the protease responsible for the cleavage of inactive pro-IL1β into active IL-1β, caspase-1, could be an alternative small molecule approach. This report describes the discovery of uracil 20, a potent (38 nM in THP1 cells assay) caspase-1 inhibitor for the topical treatment of inflammatory acne. The uracil series was designed according to a published caspase-1 pharmacophore model involving a reactive warhead in P1 for covalent reversible inhibition and an aryl moiety in P4 for selectivity against the apoptotic caspases. Reversibility was assessed in an enzymatic dilution assay or by using different substrate concentrations. In addition to classical structure-activity-relationship exploration, topical administration challenges such as phototoxicity, organic and aqueous solubility, chemical stability in solu...
A new series of nickel N,N'-dialkylimidazolidine-2,4,5-trithione complexes ([Ni(R2timdt)2]) c... more A new series of nickel N,N'-dialkylimidazolidine-2,4,5-trithione complexes ([Ni(R2timdt)2]) carrying linear or branched carbon chains (R = n-C4H9, n-C8H17, n-C12H25, n-C16H33, 2-ethylhexyl, 2-butyloctyl, phytanyl) have been obtained through an original synthetic pathway starting from easily available imidazolium-based ionic liquids. The chemical structures of these nickel complexes were confirmed by NMR and high-resolution mass spectroscopies as well as by X-ray analysis performed on single crystals. The complexes strongly absorb in the near-IR (NIR) region around 1000 nm, with high extinction coefficients reaching 80 000 M(-1) cm(-1). They are able to efficiently convert NIR light into heat under laser irradiation with very high photothermal conversion efficiencies (around 30%).
Control of band filling or doping of molecular (semi)conductors can be performed by substitutiona... more Control of band filling or doping of molecular (semi)conductors can be performed by substitutional insertion of molecules with a similar shape but a different electron count, with one more or one less electron. This strategy has been explored here within the semiconducting, single-component, radical gold dithiolene complex [AuOC4] bearing para-butoxyphenyl substituents. Alloying with the corresponding neutral nickel dithiolene complex [NiOC4] lacking one electron afforded a complete isostructural series [NiOC4]1-x[AuOC4]x, spanning the whole composition range from x = 0 to x = 1 by 0.1 increments, further characterized by X-ray diffraction and EDX analyses. Magnetic susceptibility data confirm the antiferromagnetic interactions between neighboring radical gold dithiolene complexes. The electrical conductivity increases exponentially with the x gold fraction, while the activation energy remains constant in the more conducting, gold-rich samples. This behavior is tentatively assigned to the tunneling barriers of variable width (with x) but of constant height, separating more conducting gold-rich segments. Comparison of redox potentials for the 1e(-) oxidation and reduction of both [NiOC4] and [AuOC4] dithiolene complexes indicates that the [NiOC4] nickel complex does not act as a dopant for the radical [AuOC4] complex.
Pegylated nickel-bis(dithiolene) complexes can efficiently convert NIR light into heat in water t... more Pegylated nickel-bis(dithiolene) complexes can efficiently convert NIR light into heat in water to induce cell death.
The proper functionalization of nickel bis(dithiolene) complexes by pendant cholesteryl fragments... more The proper functionalization of nickel bis(dithiolene) complexes by pendant cholesteryl fragments allows for the formation of extended networks of intertwined fibers providing robust gels. Furthermore, such nickel bis(dithiolene) complexes are also efficient photothermal centers in solution in the near infrared (NIR), with a photothermal conversion efficiency comparable to that of gold nanoparticles. This unprecedented association in one single molecule, of the two properties, i.e., gelation ability and photothermal effect, gives a highly efficient handle to modulate the gel stability through light irradiation in the NIR region, providing a novel approach to photoresponsive gels.
Nickel-bis(dithiolene) containing NPs: controlled release of Dox and photothermal therapy under N... more Nickel-bis(dithiolene) containing NPs: controlled release of Dox and photothermal therapy under NIR Irradiation.
The use of an interleukin β antibody is currently being investigated in the clinic for the treatm... more The use of an interleukin β antibody is currently being investigated in the clinic for the treatment of acne, a dermatological disorder affecting 650M persons globally. Inhibiting the protease responsible for the cleavage of inactive pro-IL1β into active IL-1β, caspase-1, could be an alternative small molecule approach. This report describes the discovery of uracil 20, a potent (38 nM in THP1 cells assay) caspase-1 inhibitor for the topical treatment of inflammatory acne. The uracil series was designed according to a published caspase-1 pharmacophore model involving a reactive warhead in P1 for covalent reversible inhibition and an aryl moiety in P4 for selectivity against the apoptotic caspases. Reversibility was assessed in an enzymatic dilution assay or by using different substrate concentrations. In addition to classical structure-activity-relationship exploration, topical administration challenges such as phototoxicity, organic and aqueous solubility, chemical stability in solu...
A new series of nickel N,N'-dialkylimidazolidine-2,4,5-trithione complexes ([Ni(R2timdt)2]) c... more A new series of nickel N,N'-dialkylimidazolidine-2,4,5-trithione complexes ([Ni(R2timdt)2]) carrying linear or branched carbon chains (R = n-C4H9, n-C8H17, n-C12H25, n-C16H33, 2-ethylhexyl, 2-butyloctyl, phytanyl) have been obtained through an original synthetic pathway starting from easily available imidazolium-based ionic liquids. The chemical structures of these nickel complexes were confirmed by NMR and high-resolution mass spectroscopies as well as by X-ray analysis performed on single crystals. The complexes strongly absorb in the near-IR (NIR) region around 1000 nm, with high extinction coefficients reaching 80 000 M(-1) cm(-1). They are able to efficiently convert NIR light into heat under laser irradiation with very high photothermal conversion efficiencies (around 30%).
Control of band filling or doping of molecular (semi)conductors can be performed by substitutiona... more Control of band filling or doping of molecular (semi)conductors can be performed by substitutional insertion of molecules with a similar shape but a different electron count, with one more or one less electron. This strategy has been explored here within the semiconducting, single-component, radical gold dithiolene complex [AuOC4] bearing para-butoxyphenyl substituents. Alloying with the corresponding neutral nickel dithiolene complex [NiOC4] lacking one electron afforded a complete isostructural series [NiOC4]1-x[AuOC4]x, spanning the whole composition range from x = 0 to x = 1 by 0.1 increments, further characterized by X-ray diffraction and EDX analyses. Magnetic susceptibility data confirm the antiferromagnetic interactions between neighboring radical gold dithiolene complexes. The electrical conductivity increases exponentially with the x gold fraction, while the activation energy remains constant in the more conducting, gold-rich samples. This behavior is tentatively assigned to the tunneling barriers of variable width (with x) but of constant height, separating more conducting gold-rich segments. Comparison of redox potentials for the 1e(-) oxidation and reduction of both [NiOC4] and [AuOC4] dithiolene complexes indicates that the [NiOC4] nickel complex does not act as a dopant for the radical [AuOC4] complex.
Pegylated nickel-bis(dithiolene) complexes can efficiently convert NIR light into heat in water t... more Pegylated nickel-bis(dithiolene) complexes can efficiently convert NIR light into heat in water to induce cell death.
The proper functionalization of nickel bis(dithiolene) complexes by pendant cholesteryl fragments... more The proper functionalization of nickel bis(dithiolene) complexes by pendant cholesteryl fragments allows for the formation of extended networks of intertwined fibers providing robust gels. Furthermore, such nickel bis(dithiolene) complexes are also efficient photothermal centers in solution in the near infrared (NIR), with a photothermal conversion efficiency comparable to that of gold nanoparticles. This unprecedented association in one single molecule, of the two properties, i.e., gelation ability and photothermal effect, gives a highly efficient handle to modulate the gel stability through light irradiation in the NIR region, providing a novel approach to photoresponsive gels.
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Papers by Kenny Mebrouk