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1.
Nat Commun ; 11(1): 3178, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576814

RESUMO

Sophisticated mechanically interlocked molecules (MIMs) with interesting structures, properties and applications have attracted great interest in the field of supramolecular chemistry. We herein report a highly efficient self-assembly of heterometallic triangular necklace 1 containing Cu and Pt metals with strong antibacterial activity. Single-crystal X-ray analysis shows that the finely arranged triangular necklace 1 has two racemic enantiomers in its solid state with intriguing packing motif. The superior antibacterial activity of necklace 1 against both standard and clinically drug-resistant pathogens implies that the presence of Cu(I) center and platinum(II) significantly enhance the bacterium-binding/damaging activity, which is mainly attributed to the highly positively charged nature, the possible synergistic effect of heterometals in the necklace, and the improved stability in culture media. This work clearly discloses the structure-property relationships that the existence of two different metal centers not only facilitates successful construction of heterometallic triangular necklace but also endows it with superior nuclease properties and antibacterial activities.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Bactérias/efeitos dos fármacos , Cobre/química , Cristalografia por Raios X , Clivagem do DNA/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Platina/química , Estereoisomerismo
2.
Chemistry ; 26(40): 8676-8688, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32452579

RESUMO

Resistance to chemotherapy is a current clinical problem, especially in the treatment of microbial infections and cancer. One strategy to overcome this is to make new derivatives of existing drugs by conjugation to organometallic fragments, either by an appropriate linker, or by direct coordination of the drug to a metal. We illustrate this with examples of conjugated organometallic metallocene sandwich and half-sandwich complexes, RuII and OsII arene, and RhIII and IrIII cyclopentadienyl half-sandwich complexes. Ferrocene conjugates are particularly promising. The ferrocene-chloroquine conjugate ferroquine is in clinical trials for malaria treatment, and a ferrocene-tamoxifen derivative (a ferrocifen) seems likely to enter anticancer trails soon. Several other examples illustrate that organometallic conjugation can restore the activity of drugs to which resistance has developed.


Assuntos
Aminoquinolinas/química , Antimaláricos/uso terapêutico , Cloroquina/farmacologia , Complexos de Coordenação/química , Compostos Ferrosos/química , Malária/tratamento farmacológico , Metalocenos/química , Compostos Organometálicos/química , Compostos de Rutênio/farmacologia , Antimaláricos/farmacologia , Cloroquina/química , Complexos de Coordenação/uso terapêutico , Humanos , Estrutura Molecular , Compostos de Rutênio/síntese química
3.
Arch Biochem Biophys ; 687: 108383, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32335048

RESUMO

Intracellular carbon monoxide (CO) is a gaseous signaling molecule and is generated enzymatically by heme oxygenases upon degradation of heme to billiverdin. Target structures for intracellular produced CO are heme proteins including cytochrome c oxidase of the respiratory chain, cytochrome P450-dependent monooxygenases, or myoglobin. For studies on CO signaling, CO-releasing molecules (CORMs) of different structure are available. Here, three frequently used CORMs (CORM-2, CORM-3 and CORM-401) were studied for their properties to provide CO in biological test systems and address susceptible heme proteins. CO release was investigated in the myoglobin binding assay and found to be rapid (<5 min) with CORM-2- and CORM-3, whereas CORM-401 continuously provided CO (>50 min). Storage stability of CORM stock solutions was also assessed with the myoglobin assay. Only CORM-401 stock solutions were stable over a period of 7 days. Incubation of CORMs with recombinant cytochrome P450 led to an inhibition of enzyme activity. However, only CORM-3 and CORM-401 proved to be suitable in this test system because controls with the inactivated CORM-2 (iCORM-2) also led to a loss of enzyme activity. The impact of CORMs on the respiratory chain was investigated with high resolution respirometry and extracellular flux technology. In the first approach interferences of CORM-2 and CORM-3 with oxygen measurement occurred, since a rapid depletion of oxygen was detected in the medium even when no cells were present. However, CORM-401 did not interfere with oxygen measurement and the expected inhibition of cellular respiration was observed. CORM-2 was not suitable for use in oxygen measurements with the extracellular flux technology and CORM-3 application did not show any effect in this system. However, CO-dependent inhibition of cellular respiration was observed with CORM-401. Based on the present experiments it is concluded, that CORM-401 produced most reliable CO-specific results for the modulation of typical CO targets. For studies on CO-dependent biological effects on intracellular heme groups, CORM-2 and CORM-3 were less suitable. Depending on the experimental setting, data achieved with these compounds should be evaluated with caution.


Assuntos
Monóxido de Carbono/metabolismo , Glicinas N-Substituídas/farmacologia , Compostos Organometálicos/farmacologia , Animais , Respiração Celular/efeitos dos fármacos , Citocromo P-450 CYP1A1/antagonistas & inibidores , Estabilidade de Medicamentos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Camundongos , Glicinas N-Substituídas/química , Compostos Organometálicos/química
4.
Nat Commun ; 11(1): 1956, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32327665

RESUMO

The dehydrogenative alkenylation of C-H bonds with alkenes represents an atom- and step-economical approach for olefin synthesis and molecular editing. Site-selective alkenylation of alkanes and aldehydes with the C-H substrate as the limiting reagent holds significant synthetic value. We herein report a photocatalytic method for the direct alkenylation of alkanes and aldehydes with aryl alkenes in the absence of any external oxidant. A diverse range of commodity feedstocks and pharmaceutical compounds are smoothly alkenylated in useful yields with the C-H partner as the limiting reagent. The late-stage alkenylation of complex molecules occurs with high levels of site selectivity for sterically accessible and electron-rich C-H bonds. This strategy relies on the synergistic combination of direct hydrogen atom transfer photocatalysis with cobaloxime-mediated hydrogen-evolution cross-coupling, which promises to inspire additional perspectives for selective C-H functionalizations in a green manner.


Assuntos
Aldeídos/química , Alcanos/química , Alcenos/química , Alcenos/síntese química , Catálise , Técnicas de Química Sintética , Química Verde , Estrutura Molecular , Compostos Organometálicos/química , Processos Fotoquímicos , Estereoisomerismo
5.
Chemistry ; 26(27): 6056-6063, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32133687

RESUMO

The properties of LnIII -HPDO3A complexes as relaxation enhancers and paraCEST agents are essentially related to the hydroxylpropyl moiety. A series of three HPDO3A derivatives, with small modifications to the hydroxyl arm, were herein investigated to understand how heightened control can be gained over the parameters involved in the design of these agents. A full 1 H and 17 O-NMR relaxometric analysis was conducted and demonstrated that increasing the length of the OH group from the lanthanide centre significantly enhanced the water exchange rate of the gadolinium complex, but with a subsequent reduction in kinetic stability. Alternatively, the introduction of an additional methyl group, which increased the steric bulk around the OH moiety, resulted in the formation of almost exclusively the TSAP isomer (95 %) as identified by 1 H-NMR of the europium complex. The gadolinium analogue of this complex also exhibited a very fast water exchange rate, but with no detectable loss of kinetic stability. This complex therefore demonstrates a notable improvement over Gd-HPDO3A.


Assuntos
Meios de Contraste/química , Gadolínio/química , Elementos da Série dos Lantanídeos/química , Imagem por Ressonância Magnética/métodos , Európio/química , Compostos Heterocíclicos/química , Cinética , Compostos Organometálicos/química , Água
6.
J Photochem Photobiol B ; 204: 111811, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32028187

RESUMO

The development of multidrug resistance is often associated with the over-expression of P-glycoprotein (P-gp). This protein prevents drug accumulation and extrudes them out of the cell before they reach the intended target. The aim of this study was to develop an in vitro MCF-7 cell line with increased expression of P-gp and test the phototoxicity of a novel photoactivated zinc phthalocyanine tetrasulfonic acid (ZnPcS4) on these cells. The over-expressed P-gp MCF-7 cells (MCF-7/DOX) were developed from wildtype (WT) MCF-7 cells by a stepwise continuous exposure of the WT cells to different concentrations of Doxorubicin (DOX) (0.1 - 1 µM) over a period of 4 months. The P-gp expression was measured using flow cytometry, immunofluorescence and enzyme immunoassay. To verify whether zinc phthalocyanine-mediated photodynamic therapy (ZnPcS4 - PDT) is effective in MCF-7/DOX, we studied the subcellular localization, phototoxicity and nuclear damage. The flow cytometry result showed two distinct peaks of P-gp positive and negative expression in MCF-7/DOX cell population, which correlates with the ELISA-based assay (p˂0.001). The ME16C (Normal breast cells) was used as control. The localization studies showed that ZnPcS4 have greater affinity for lysosome than mitochondria. Phototoxicity results indicated that photoactivated zinc phthalocyanine decreased the cell proliferation and viability as the drug and laser light dosages increased to 16 µM and 20 J/cm2 respectively. PDT-induced cytotoxicity using lactose dehydrogenase (LDH) enzyme leakage as measure did not increase likewise. The ZnPcS4-induced PDT was less effective for MCF-7/DOX cells which could be attributed to decreased retention of ZnPcS4 in major cellular organelles due to the presence of increased drug efflux P-gp. The current findings suggest that, increased P-gp expression, a characteristic of multidrug resistance together with other related intrinsic mechanisms might contribute to render MCF-7/DOX cells less sensitive to ZnPcS4-induced phototoxicity.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Proliferação de Células/efeitos dos fármacos , Indóis/farmacologia , Lasers Semicondutores , Compostos Organometálicos/farmacologia , Trifosfato de Adenosina/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos da radiação , Feminino , Humanos , Indóis/química , Células MCF-7 , Compostos Organometálicos/química , Fotoquimioterapia , Rodamina 123/química , Rodamina 123/metabolismo
7.
Chem Commun (Camb) ; 56(20): 3065-3068, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32049076

RESUMO

Herein, a novel stacked hexagonal prism, Ag@Ni-MOF-1, was designed and developed as an integrated SERS platform not only for successfully catalyzing the in situ synthesis of DA-quinone under physiological pH, but also for establishing an approach for specific determination of Cys, an important species in the brain related to Alzheimer's disease (AD).


Assuntos
Benzoquinonas/síntese química , Materiais Biomiméticos/química , Dopamina/síntese química , Níquel/química , Compostos Organometálicos/química , Prata/química , Benzoquinonas/química , Catálise , Cisteína/análise , Dopamina/química , Humanos , Concentração de Íons de Hidrogênio , Compostos Organometálicos/síntese química , Análise Espectral Raman
8.
Int J Nanomedicine ; 15: 137-149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021170

RESUMO

Purpose: Traditional chemotherapy is accompanied by significant side effects, which, in many aspects, limits its treatment efficacy and clinical applications. Herein, we report an oxidative responsive polymersome nanosystem mediated by near infrared (NIR) light which exhibited the combination effect of photodynamic therapy (PDT) and chemotherapy. Methods: In our study, poly (propylene sulfide)20-bl-poly (ethylene glycol)12 (PPS20-b-PEG12) block copolymer was synthesized and employed to prepare the polymersome. The hydrophobic photosensitizer zinc phthalocyanine (ZnPc) was loaded in the shell and the hydrophilic doxorubicin hydrochloride (DOX·HCl) in the inner aqueous space of the polymersome. Results: Under the irradiation of 660 nm NIR light, singlet oxygen 1O2 molecules were generated from ZnPc to oxidize the neighbouring sulfur atoms on the PPS block which eventually ruptured the intact structure of polymersomes, leading to the release of encapsulated DOX·HCl. The released DOX and the 1O2 could achieve a combination effect for cancer therapy if the laser activation and drug release occur at the tumoral sites. In vitro studies confirmed the generation of singlet oxygen and DOX release by NIR irradiation. In vivo studies showed that such a combined PDT-chemotherapy nanosystem could accumulate in A375 tumors efficiently, thus leading to significant inhibition on tumor growth as compared to PDT (PZ group) or chemotherapy alone (DOX group). Conclusion: In summary, this oxidation-sensitive nanosystem showed excellent anti-tumor effects by synergistic chemophotodynamic therapy, indicating that this novel drug delivery strategy could potentially provide a new means for cancer treatments in clinic.


Assuntos
Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Melanoma Experimental/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Doxorrubicina/farmacocinética , Liberação Controlada de Fármacos , Humanos , Indóis/administração & dosagem , Indóis/química , Lasers , Masculino , Camundongos Endogâmicos BALB C , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/química , Polietilenoglicóis/química , Polímeros/química , Oxigênio Singlete/farmacocinética , Sulfetos/química
9.
Food Chem ; 317: 126434, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32106007

RESUMO

A triazole-stabilized fluorescence sensor is developed for copper detection in the study. Tris-(benzyltriazolylmethyl)amine (TBTA) is used to improve the sensitivity and stability for the sensing system. A series of comparative experiments are performed with and without TBTA. In the presence of TBTA, the fluorescence decrease ratio is enhanced from 2.46 to 118.25; the detection limit is reduced from 67 nM to 3.6 nM; the higher selectivity toward copper compared to the other metal ions is verified, including K+, Ca2+, Cd2+, Zn2+, Mg2+, Mn2+, Pb2+, Hg2+, Fe3+ and Cr3+. Besides, the sensing system is successfully applied for copper determination in complex tea samples and chicken feed samples with the recovery range of 91.67-116.8%. A good consistency between the presented sensor and the flame atom absorbance spectrometry (FAAS) is confirmed by the low relative errors with the range from -2.39% to 7.02%.


Assuntos
Ração Animal/análise , Cobre/análise , Análise de Alimentos/métodos , Espectrometria de Fluorescência/métodos , Chá/química , Fluorescência , Corantes Fluorescentes/química , Limite de Detecção , Metais/análise , Compostos Organometálicos/química , Sensibilidade e Especificidade , Triazóis/química
10.
Yakugaku Zasshi ; 140(2): 273-287, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32009047

RESUMO

Our investigations of various aspects of organic chemistry over the past 43 years are reviewed in this paper. The following subjects are discussed: 1) the diastereoselective addition reaction to chiral imines and oxazolidines of organometallic reagents and its applications and 2) the reaction and synthesis of fluorine-containing compounds.


Assuntos
Química Orgânica/tendências , Compostos de Flúor/síntese química , Iminas/química , Compostos Organometálicos/química , Oxazóis/química , Estereoisomerismo , Fatores de Tempo
11.
Dalton Trans ; 49(10): 3042-3087, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32048663

RESUMO

Metallopolymers (MPs) or metal-containing polymers have shown great potential as self-healing and shape memory materials due to their unique characteristics, including universal architectures, composition, properties and surface chemistry. Over the past few decades, the exponential growth of many new classes of MPs that deal with these issues has been demonstrated. This review presents and assesses the latest achievements and problems associated with the use of MPs as self-healing and shape memory materials. Among the most widely used MPs with self-healing properties, metal complexes based on polymers containing phenol, carboxylic acid, pyridine, azole, histidine and urethane donor fragments are identified. Particular attention is paid to the principles of action of the shape memory MPs. Of considerable interest is the use of MPs as functional materials for sensors, soft electronic devices, transistors, conductors, nanogenerators, bone tissue engineering, etc. Finally, the problems and future prospects of MPs with self-healing and shape memory properties are outlined. This review also analyzes articles published over the past five years.


Assuntos
Compostos Organometálicos/química , Polímeros/química , Ligantes , Metais/química
12.
Dalton Trans ; 49(8): 2412-2416, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32022076

RESUMO

The interactions between the cytotoxic paddlewheel dirhodium complex [Rh2(µ-O2CCH3)4] and the model protein bovine pancreatic ribonuclease (RNase A) were investigated by high-resolution mass spectrometry and X-ray crystallography. The results indicate that [Rh2(µ-O2CCH3)4] extensively reacts with RNase A. The metal compound binds the protein via coordination of the imidazole ring of a His side chain to one of its axial sites, while the dirhodium center and the acetato ligands remain unmodified. Data provide valuable information for the design of artificial dirhodium-containing metalloenzymes.


Assuntos
Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Ribonuclease Pancreático/química , Ribonuclease Pancreático/metabolismo , Animais , Bovinos , Cristalografia por Raios X , Ligantes , Modelos Moleculares , Conformação Proteica
13.
Chem Commun (Camb) ; 56(9): 1397-1400, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31912815

RESUMO

NAMI-A is highly reactive to Sp1, a tumor metastasis related protein, resulting in the perturbation of the protein structure and disruption of the DNA recognition of Sp1. Interestingly, Sp1 is more susceptible than other zinc finger proteins to NAMI-A, suggesting that Sp1 could be the anti-metastasis target of NAMI-A.


Assuntos
Antineoplásicos/química , Dimetil Sulfóxido/análogos & derivados , Compostos Organometálicos/química , Compostos de Rutênio/química , Fator de Transcrição Sp1/química , DNA/metabolismo , Dimetil Sulfóxido/química , Glutationa/química , Ligação Proteica , Multimerização Proteica/efeitos dos fármacos , Estrutura Secundária de Proteína/efeitos dos fármacos , Desdobramento de Proteína/efeitos dos fármacos , Fator de Transcrição Sp1/metabolismo
14.
Chemistry ; 26(8): 1697, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31922634

RESUMO

Invited for the cover of this issue is the group of Torres at the University of Madrid. The image of the cover of this issue depicts cancer cells being destroyed by reactive singlet oxygen produced by ruthenium phthalocyanine glycoconjugates under red light. The work, developed at the Universities of Madrid, Aveiro, Lisbon and Coimbra, describes ruthenium phthalocyanines as powerful bladder cancer PDT agents. Read the full text of the article at 10.1002/chem.201903546.


Assuntos
Compostos Organometálicos/química , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/metabolismo , Humanos , Compostos Organometálicos/síntese química , Compostos Organometálicos/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico
15.
Chem Rev ; 120(3): 1513-1619, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31904936

RESUMO

This review describes the additions of allylmagnesium reagents to carbonyl compounds and to imines, focusing on the differences in reactivity between allylmagnesium halides and other Grignard reagents. In many cases, allylmagnesium reagents either react with low stereoselectivity when other Grignard reagents react with high selectivity, or allylmagnesium reagents react with the opposite stereoselectivity. This review collects hundreds of examples, discusses the origins of stereoselectivities or the lack of stereoselectivity, and evaluates why selectivity may not occur and when it will likely occur.


Assuntos
Álcoois/síntese química , Aldeídos/química , Compostos Alílicos/química , Cetonas/química , Magnésio/química , Compostos Organometálicos/química , Estereoisomerismo
16.
Chem Rev ; 120(4): 1981-2048, 2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-31967451

RESUMO

In this contribution, we provide a comprehensive overview of C-H activation methods promoted by NHC-transition metal complexes, covering the literature since 2002 (the year of the first report on metal-NHC-catalyzed C-H activation) through June 2019, focusing on both NHC ligands and C-H activation methods. This review covers C-H activation reactions catalyzed by group 8 to 11 NHC-metal complexes. Through discussing the role of NHC ligands in promoting challenging C-H activation methods, the reader is provided with an overview of this important area and its crucial role in forging carbon-carbon and carbon-heteroatom bonds by directly engaging ubiquitous C-H bonds.


Assuntos
Técnicas de Química Sintética/métodos , Compostos Heterocíclicos/química , Metano/análogos & derivados , Compostos Organometálicos/química , Paládio/química , Compostos Heterocíclicos/síntese química , Imidazóis/química , Metano/química , Oxazóis/química , Tiazóis/química
17.
Molecules ; 25(2)2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31936003

RESUMO

: A series of free base and Zn(II) phthalocyanines featuring fluorenyl antennae linked by methoxy or oxo bridges to the phthalocyanine core (Pc) were synthesized and characterized. Selected linear and nonlinear (two-photon absorption) optical properties of these new compounds were subsequently studied. As previously observed for related porphyrin dendrimers bearing 2-fluorenyl peripheral dendrons, an efficient energy transfer occurs from the peripheral antennae to the central phthalocyanine core following excitation in the fluorenyl-based π-π* absorption band of these chromophores. Once excited, these compounds relax to the ground state, mostly by emitting intense red light or by undergoing intersystem crossing. As a result, the tetrafunctionalized Zn(II) phthalocyanines are fluorescent, but can also efficiently photosensitize molecular oxygen in tetrahydrofurane (THF), forming singlet oxygen with nearly comparable yields to bare Zn(II) phthalocyanine (ZnPc). In comparison with the latter complex, the positive role of the fluorenyl-containing antennae on one- and two-photon brightness (2PA) is presently demonstrated when appended in peripheral (ß) position to the phthalocyanine core. Furthermore, when compared to known porphyrin analogues, the interest in replacing the porphyrin by a phthalocyanine as the central core to obtain more fluorescent two-photon oxygen photosensitizers is clearly established. As such, this contribution paves the way for the future development of innovative biphotonic photosensitizers usable in theranostics.


Assuntos
Fluorenos/química , Indóis/química , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/química , Transferência de Energia , Fluorenos/síntese química , Indóis/síntese química , Luz , Luminescência , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Fótons , Porfirinas/química , Oxigênio Singlete/isolamento & purificação , Análise Espectral
18.
Molecules ; 25(2)2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31936104

RESUMO

Metallation of biomacromolecular species forms the basis for the anticancer activity of many metallodrugs. A major limitation of these compounds is that their reactivity is indiscriminate and can, in principle, occur in healthy tissue as well as cancerous tissue, potentially leading to side effects in vivo. Here we present pH-dependent intramolecular coordination of an arene-tethered sulfonamide functionality in organometallic ruthenium(II) ethylenediamine complexes as a route to controlling the coordination environment about the central metal atom. Through variation of the sulfonamide R group and the length of the tether linking it to the arene ligand the acidity of the sulfonamide NH group, and hence the pH-region over which regulation of metal coordination occurs, can be modulated. Intramolecular sulfonamide ligation controlled the reactivity of complex 4 within the physiologically relevant pH-region, rendering it more reactive towards 5'-GMP in mildly acidic pH-conditions typical of tumour tissue compared to the mildly alkaline pH-conditions typical of healthy tissue. However, the activation of 4 by ring-opening of the chelate was found to be a slow process relative to the timescale of typical cell culture assays and members of this series of complexes were found not to be cytotoxic towards the HT-29 cell line. These complexes provide the basis for the development of analogues of increased potency where intramolecular sulfonamide ligation regulates reactivity and therefore cytotoxicity in a pH-dependent, and potentially, tissue-dependent manner.


Assuntos
Antineoplásicos/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Diaminas/química , Compostos Organometálicos/farmacologia , Rutênio/química , Sulfonamidas/química , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Quelantes/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/toxicidade , Cristalografia por Raios X , Diaminas/farmacologia , Etilenodiaminas/química , Etilenodiaminas/farmacologia , Guanosina Monofosfato/metabolismo , Células HT29 , Humanos , Concentração de Íons de Hidrogênio , Cinética , Ligantes , Modelos Moleculares , Compostos Organometálicos/química , Rutênio/farmacologia , Sulfonamidas/farmacologia
19.
Molecules ; 25(2)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936557

RESUMO

Synthesis of new chromium(II) complexes with chelating bis(alkoxide) ligand [OO]Ph (H2[OO]Ph = [1,1':4',1''-terphenyl]-2,2''-diylbis(diphenylmethanol)) and their subsequent reactivity in the context of catalytic production of carbodiimides from azides and isocyanides are described. Two different Cr(II) complexes are obtained, as a function of the crystallization solvent: mononuclear Cr[OO]Ph(THF)2 (in toluene/THF, THF = tetrahydrofuran) and dinuclear Cr2([OO]Ph)2 (in CH2Cl2/THF). The electronic structure and bonding in Cr[OO]Ph(THF)2 were probed by density functional theory calculations. Isolated Cr2([OO]Ph)2 undergoes facile reaction with 4-MeC6H4N3, 4-MeOC6H4N3, or 3,5-Me2C6H3N3 to yield diamagnetic Cr(VI) bis(imido) complexes; a structure of Cr[OO]Ph(N(4-MeC6H4))2 was confirmed by X-ray crystallography. The reaction of Cr2([OO]Ph)2 with bulkier azides N3R (MesN3, AdN3) forms paramagnetic products, formulated as Cr[OO]Ph(NR). The attempted formation of a Cr-alkylidene complex (using N2CPh2) instead forms chromium(VI) bis(diphenylmethylenehydrazido) complex Cr[OO]Ph(NNCPh2)2. Catalytic formation of carbodiimides was investigated for the azide/isocyanide mixtures containing various aryl azides and isocyanides. The formation of carbodiimides was found to depend on the nature of organoazide: whereas bulky mesitylazide led to the formation of carbodiimides with all isocyanides, no carbodiimide formation was observed for 3,5-dimethylphenylazide or 4-methylphenylazide. Treatment of Cr2([OO]Ph)2 or H2[OO]Ph with NO+ leads to the formation of [1,2-b]-dihydroindenofluorene, likely obtained via carbocation-mediated cyclization of the ligand.


Assuntos
Quelantes/química , Cromo/química , Compostos Organometálicos/química , Alcanos/química , Azidas/química , Catálise , Quelantes/síntese química , Cristalografia por Raios X , Ligantes , Estrutura Molecular , Compostos Organometálicos/síntese química
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