The controlled release of biologically active species from diruthenium compounds is crucial for the devel-opment of selective drug delivery systems based on such complexes,which in addition display antineo-plastic pro...The controlled release of biologically active species from diruthenium compounds is crucial for the devel-opment of selective drug delivery systems based on such complexes,which in addition display antineo-plastic properties by themselves.In the present work,we analyse in detail the kinetics of the pH-triggered release of the auxin-related hormones 2,4-D(2,4-dichlorophenoxyacetate)and NAA(1-naphthaleneace-tate)from the metal–metal bonded tris(formamidinato)Ru_(2)^(5+)complexes[Ru_(2)Cl(μ-DPhF)_(3)(μ-2,4-D)](Ru_(2),4-D),[Ru_(2)Cl(μ-DPhF)_(3)(μ-NAA)](RuNAA),[Ru_(2)Cl(μ-DAniF)_(3)(μ-2,4-D)](Ru’2,4-D)and[Ru_(2)Cl(μ-DAniF)_(3)(μ-NAA)](Ru’NAA)(DPhF=N,N’-diphenylformamidinate,DAniF=N,N’-bis(p-methoxy)phenylfor-mamidinate).Moreover,the synthesis and complete characterisation of[Ru_(2)Cl(μ-DAniF)_(3)(μ-IAA)](Ru’IAA,IAA=indole-3-acetate),Ru’2,4-D and Ru’NAA,including the crystal structure of the two latter ones,is reported.The release of auxins is studied through a fluorimetric quantitative assay,which allows deter-mining the influence of different formamidinate ancillary ligands and the nature of the outgoing auxin ligand in the release process.Chemometrics is employed to evaluate the statistical significance of the variables.The release of auxins is slower at physiological pH and occurs faster at slightly acidic pH values.Compounds containing DPhF ancillary ligands and NAA outgoing ligand present a slower dissociation of the auxin,which is not complete in the first 24 h.The release rate is also correlated with the bond dis-tance O1(auxin)–Ru1(hexacoordinated).A mechanism of the substitution reaction is tentatively proposed based on these findings.Overall,these results pave the way towards new systems for the controlled deliv-ery of antineoplastic drugs under mild-acidic conditions like those surrounding solid tumours.展开更多
Metastasis is a major health threat for most cancer patients,thus anti-metastasis treatments that reduce cell migration and invasion are critical for cancer treatment. In this study,four anthraquinone-bridged diruthen...Metastasis is a major health threat for most cancer patients,thus anti-metastasis treatments that reduce cell migration and invasion are critical for cancer treatment. In this study,four anthraquinone-bridged diruthenium(Ⅱ) complexes,[(bpy)_(2)Ru(L)Ru(bpy)_(2)]^(4+) (Ru1,L=1,4-bis(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)anthracene-9,10-dione;Ru2,L=1,5-bis(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)anthracene-9,10-dione;Ru3,L=2,6-bis(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)anthracene-9,10-dione;and Ru4,L=2,7-bis(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)anthracene-9,10-dione) were synthesized and characterized. These Ru(Ⅱ) complexes exhibited multi-targeted anti-metastatic properties against human hepatocarcinoma MHCC97-H cells that included the inhibition of migration and invasion. Further investigation of the intracellular mechanisms revealed that Ru(Ⅱ) complexes suppressed the phosphorylation of ERK and AKT. Moreover,significant reduction of the extracellular and intracellular expression of the metastatic regulatory proteins MMP-2 and MMP-9 was also observed after Ru1–Ru4 treatment. In addition,these Ru(Ⅱ) complexes negatively modulate the actin cytoskeleton by inhibiting Cdc42 protein expression,arresting the cells in the G2/M phase. The results indicate that these ruthenium(Ⅱ) complexes have potential as drug candidates for anti-metastatic therapies.展开更多
This article provides an overview of the application of diruthenium(Ⅱ,Ⅲ)paddlewheel complexes for anticancer purposes.The use of this coordinative construct is indeed attractive because it provides an excellent oppo...This article provides an overview of the application of diruthenium(Ⅱ,Ⅲ)paddlewheel complexes for anticancer purposes.The use of this coordinative construct is indeed attractive because it provides an excellent opportunity to combine the pharmacological properties of the dimetallic ruthenium center with those derived from the specific choice of ligands bearing a carboxylic function capable of coordination towards the Ru-Ru core.展开更多
A cyclometalated diruthenium complex 2 bridged by 1,2,4,5-tetra(pyrid-2-yl)benzene with six carboxylic acid groups at two ends was synthesized.Monolayer and multilayer films FTO/TiO2/(2)n(Zr)(n=1,2)and FTO/SnO2:Sb/(2)...A cyclometalated diruthenium complex 2 bridged by 1,2,4,5-tetra(pyrid-2-yl)benzene with six carboxylic acid groups at two ends was synthesized.Monolayer and multilayer films FTO/TiO2/(2)n(Zr)(n=1,2)and FTO/SnO2:Sb/(2)n(Zr)(n=1-4)have been prepared via interfacial layer-by-layer coordination assembly of 2 with zirconium(IV)ions.All films show two consecutive redox couples in the potential range between 0 and+1.0 V vs.Ag/AgCl.These films exhibit reversible near-infrared electrochromism upon switching of redox potential.The response time of the films on SnO2:Sb is around a few seconds,while that on TiO2 is around a few tens of seconds.The film deposition cycles were found to have a great impact on the electrochromic performance.Among six films examined,the two-layered film on SnO2:Sb displays the best balanced performance with a contrast ratio of 56%at 1,150 nm and good cyclic stability(9%loss of contrast ratio after 1,000 continuous double-potential-switching cycles),which is superior to that of the previously reported electropolymerized films of a related diruthenium complex with the same bridging ligand.In addition,the X-ray photoelectron spectroscopy,scanning electron microscopy,and electron transfer mechanism of these films have been investigated.展开更多
基金funded by Comunidad de Madrid(B2017/BMD-3770-CM)to S.H.the Spanish Ministry of Science and Innovation(RTI2018-094793-B-I00)to C.G.+1 种基金by institutional grants from Fundación Ramón Areces and Banco de Santander to the Centro de Biología Molecular Severo OchoaI.C.acknowl-edges a predoctoral grant(CT82/20-CT83/20)from Complutense University of Madrid and Banco de Santander.
文摘The controlled release of biologically active species from diruthenium compounds is crucial for the devel-opment of selective drug delivery systems based on such complexes,which in addition display antineo-plastic properties by themselves.In the present work,we analyse in detail the kinetics of the pH-triggered release of the auxin-related hormones 2,4-D(2,4-dichlorophenoxyacetate)and NAA(1-naphthaleneace-tate)from the metal–metal bonded tris(formamidinato)Ru_(2)^(5+)complexes[Ru_(2)Cl(μ-DPhF)_(3)(μ-2,4-D)](Ru_(2),4-D),[Ru_(2)Cl(μ-DPhF)_(3)(μ-NAA)](RuNAA),[Ru_(2)Cl(μ-DAniF)_(3)(μ-2,4-D)](Ru’2,4-D)and[Ru_(2)Cl(μ-DAniF)_(3)(μ-NAA)](Ru’NAA)(DPhF=N,N’-diphenylformamidinate,DAniF=N,N’-bis(p-methoxy)phenylfor-mamidinate).Moreover,the synthesis and complete characterisation of[Ru_(2)Cl(μ-DAniF)_(3)(μ-IAA)](Ru’IAA,IAA=indole-3-acetate),Ru’2,4-D and Ru’NAA,including the crystal structure of the two latter ones,is reported.The release of auxins is studied through a fluorimetric quantitative assay,which allows deter-mining the influence of different formamidinate ancillary ligands and the nature of the outgoing auxin ligand in the release process.Chemometrics is employed to evaluate the statistical significance of the variables.The release of auxins is slower at physiological pH and occurs faster at slightly acidic pH values.Compounds containing DPhF ancillary ligands and NAA outgoing ligand present a slower dissociation of the auxin,which is not complete in the first 24 h.The release rate is also correlated with the bond dis-tance O1(auxin)–Ru1(hexacoordinated).A mechanism of the substitution reaction is tentatively proposed based on these findings.Overall,these results pave the way towards new systems for the controlled deliv-ery of antineoplastic drugs under mild-acidic conditions like those surrounding solid tumours.
基金supported by the 973 Program(no.2015CB856301)the National Science Foundation of China(no.21471164 and 21525105)+2 种基金Guangdong Province Public Research and Capacity-Building of Special Foundation(no.2015A020211037)Guangzhou Science and Technology Project(no.201607010087)the Natural Science Foundation of Guangdong Province(no.2016A030310298).
文摘Metastasis is a major health threat for most cancer patients,thus anti-metastasis treatments that reduce cell migration and invasion are critical for cancer treatment. In this study,four anthraquinone-bridged diruthenium(Ⅱ) complexes,[(bpy)_(2)Ru(L)Ru(bpy)_(2)]^(4+) (Ru1,L=1,4-bis(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)anthracene-9,10-dione;Ru2,L=1,5-bis(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)anthracene-9,10-dione;Ru3,L=2,6-bis(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)anthracene-9,10-dione;and Ru4,L=2,7-bis(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)anthracene-9,10-dione) were synthesized and characterized. These Ru(Ⅱ) complexes exhibited multi-targeted anti-metastatic properties against human hepatocarcinoma MHCC97-H cells that included the inhibition of migration and invasion. Further investigation of the intracellular mechanisms revealed that Ru(Ⅱ) complexes suppressed the phosphorylation of ERK and AKT. Moreover,significant reduction of the extracellular and intracellular expression of the metastatic regulatory proteins MMP-2 and MMP-9 was also observed after Ru1–Ru4 treatment. In addition,these Ru(Ⅱ) complexes negatively modulate the actin cytoskeleton by inhibiting Cdc42 protein expression,arresting the cells in the G2/M phase. The results indicate that these ruthenium(Ⅱ) complexes have potential as drug candidates for anti-metastatic therapies.
基金support of the Italian Ministry of Research(MUR).
文摘This article provides an overview of the application of diruthenium(Ⅱ,Ⅲ)paddlewheel complexes for anticancer purposes.The use of this coordinative construct is indeed attractive because it provides an excellent opportunity to combine the pharmacological properties of the dimetallic ruthenium center with those derived from the specific choice of ligands bearing a carboxylic function capable of coordination towards the Ru-Ru core.
基金supported by the National Natural Science Foundation of China (21872154), Beijing National Science Foundation (2191003)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB12010400)
文摘A cyclometalated diruthenium complex 2 bridged by 1,2,4,5-tetra(pyrid-2-yl)benzene with six carboxylic acid groups at two ends was synthesized.Monolayer and multilayer films FTO/TiO2/(2)n(Zr)(n=1,2)and FTO/SnO2:Sb/(2)n(Zr)(n=1-4)have been prepared via interfacial layer-by-layer coordination assembly of 2 with zirconium(IV)ions.All films show two consecutive redox couples in the potential range between 0 and+1.0 V vs.Ag/AgCl.These films exhibit reversible near-infrared electrochromism upon switching of redox potential.The response time of the films on SnO2:Sb is around a few seconds,while that on TiO2 is around a few tens of seconds.The film deposition cycles were found to have a great impact on the electrochromic performance.Among six films examined,the two-layered film on SnO2:Sb displays the best balanced performance with a contrast ratio of 56%at 1,150 nm and good cyclic stability(9%loss of contrast ratio after 1,000 continuous double-potential-switching cycles),which is superior to that of the previously reported electropolymerized films of a related diruthenium complex with the same bridging ligand.In addition,the X-ray photoelectron spectroscopy,scanning electron microscopy,and electron transfer mechanism of these films have been investigated.
