- Application of cyclometalated rhodium(III) complexes as therapeutic agents in biomedical and luminescent cellular imaging
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The synthesis and characterization of three [Rh(ppy)2(N^N)][PF6] complexes, [Rh(ppy)2(pybtz)][PF6].CH3OH (Rh1), [Rh(ppy)2(pzbtz)][PF6] (Rh2) and [Rh(ppy)2(qbtz)][PF6] (Rh3) [Hppy: 2-phenylpyridine; N^N: (pyridin-2-yl)benzo[d]thiazole (pybtz), (pyrazin-2-yl)benzo[d]thiazole (pzbtz), and (quinolin-2-yl)benzo[d]thiazole (qbtz)], and single crystal structures of Rh1 and Rh3 are reported. Rh1 and Rh3 show high fluorescent intensities upon excitation at 400 and 410 nm, respectively. Evaluation of lipophilicity by theoretical calculations indicates Rh3 > Rh1 > Rh2, introducing Rh3 as the best candidate for biological studies. The Rh3 exhibits anticancer activity, with high cellular uptake efficiency and good cytotoxicity against MCF-7 cell line as compared to the non-malignant MRC-5 cells. Flow cytometry have confirmed the apoptosis cell death and cell cycle arrest in the sub-G1 phase. The result of real time PCR shows that Rh3 induces apoptosis by up-regulating of p53, miR-15a, miR-16–1 and miR-29b and down regulating of bcl-2 and miR-21 at the level of RNA transcription. Importantly, cell imaging experiments have demonstrated that Rh3 can be considered as a new promising metallodrug candidate for cancer treatment.
- Amiri, Ahmad,Amirnasr, Mehdi,Bikhof Torbati, Maryam,Farrokhpour, Hossein,Lutz, Martin,Meghdadi, Soraia,Sohrabi, Marzieh
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- New Pyrazine Conjugates: Synthesis, Computational Studies, and Antiviral Properties against SARS-CoV-2
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Currently, limited therapeutic options are available for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We have developed a set of pyrazine-based small molecules. A series of pyrazine conjugates was synthesized by microwave-assisted click chemistry and benzotriazole chemistry. All the synthesized conjugates were screened against the SAR-CoV-2 virus and their cytotoxicity was determined. Computational studies were carried out to validate the biological data. Some of the pyrazine-triazole conjugates (5 d–g) and (S)-N-(1-(benzo[d]thiazol-2-yl)-2-phenylethyl)pyrazine-2-carboxamide 12 i show significant potency against SARS-CoV-2 among the synthesized conjugates. The selectivity index (SI) of potent conjugates indicates significant efficacy compared to the reference drug (Favipiravir).
- Seliem, Israa A.,Girgis, Adel S.,Moatasim, Yassmin,Kandeil, Ahmed,Mostafa, Ahmed,Ali, Mohamed A.,Bekheit, Mohamed S.,Panda, Siva S.
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p. 3418 - 3427
(2021/09/08)
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- Pd-Catalyzed Decarbonylative C?H Coupling of Azoles and Aromatic Esters
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A decarbonylative C?H coupling of azoles and aromatic esters by palladium catalysis is described. Our previously reported Ni-catalyzed C?H coupling of azoles and aromatic esters has a significant drawback regarding the substrate scope. Herein, we employ p
- Matsushita, Kaoru,Takise, Ryosuke,Hisada, Tomoya,Suzuki, Shin,Isshiki, Ryota,Itami, Kenichiro,Muto, Kei,Yamaguchi, Junichiro
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supporting information
p. 2393 - 2396
(2018/05/30)
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- Development of (quinolinyl)amido-based pincer palladium complexes: A robust and phosphine-free catalyst system for C-H arylation of benzothiazoles
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(Quinolinyl)amido-ligated palladium(ii) complexes have been synthesized and applied in the catalytic C-H bond arylation of benzothiazoles. The tridentate ligand precursors R2N-C(O)CH2-(NH)-C9H6N [(R2NNN8-Q)-H; R2N = morpholinyl, Me-N-piperazinyl] and the pincer palladium complexes [κN,κN,κN-{R2N-C(O)CH2-(μ-N)-C9H6N}]PdX [(R2NNN8-Q)PdX {R2N = Et2N, morpholinyl, Me-N-piperazinyl; X = OAc or Cl}] were efficiently synthesized, and characterized by various analytical techniques. The iodo derivative (Et2NNN8-Q)PdI was obtained in excellent yield by the treatment of the complex (Et2NNN8-Q)PdCl with KI. The molecular structures of complexes (Et2NNN8-Q)Pd(OAc) (2a), (Et2NNN8-Q)PdCl (3a) and (Et2NNN8-Q)PdI (4a) were elucidated by X-ray crystallography. Complex 3a was found to be the most efficient catalyst for direct C-H bond arylation of substituted benzothiazoles with diverse aryl iodides using a mild base, K2CO3. The working catalyst system 3a is highly robust and can be recycled and reused several times for the arylation of benzothiazole without loss of catalytic activity. Preliminary mechanistic investigations using controlled studies and kinetic analysis have been performed, which greatly support a molecular mechanism for the arylation.
- Pandiri, Hanumanprasad,Soni, Vineeta,Gonnade, Rajesh G.,Punji, Benudhar
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p. 3543 - 3554
(2017/07/12)
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- Mechanistic Insights into Pincer-Ligated Palladium-Catalyzed Arylation of Azoles with Aryl Iodides: Evidence of a PdII-PdIV-PdII Pathway
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Pincer-based (R2POCNR′2)PdCl complexes along with CuI cocatalyst catalyze the arylation of azoles with aryl iodides to give the 2-arylated azole products. Herein, we report an extensive mechanistic investigation for the direct arylation of azoles involving a well-defined and highly efficient (iPr2POCNEt2)PdCl (2a) catalyst, which emphasizes a rare PdII-PdIV-PdII redox catalytic pathway. Kinetic studies and deuterium labeling experiments indicate that the C-H bond cleavage on azoles occurs via two distinct routes in a reversible manner. Controlled reactivity of the catalyst 2a underlines the iodo derivative (iPr2POCNEt2)PdI (3a) to be the resting state of the catalyst. The intermediate species (iPr2POCNEt2)Pd-benzothiazolyl (4a) has been isolated and structurally characterized. A determination of reaction rates of compound 4a with electronically different aryl iodides has revealed the kinetic significance of the oxidative addition of the C(sp2)-X electrophile, aryl iodide, to complex 4a. Furthermore, the reactivity behavior of 4a suggests that the arylation of benzothiazole proceeds via an oxidative addition/reductive elimination pathway involving a (iPr2POCNEt2)PdIV(benzothiazolyl)(Ar)I species, which is strongly supported by DFT calculations.
- Khake, Shrikant M.,Jagtap, Rahul A.,Dangat, Yuvraj B.,Gonnade, Rajesh G.,Vanka, Kumar,Punji, Benudhar
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supporting information
p. 875 - 886
(2016/04/19)
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- Design and development of POCN-pincer palladium catalysts for C-H bond arylation of azoles with aryl iodides
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Well-defined and efficient POCN-ligated palladium complexes have been developed for the direct C-H bond arylation of azoles with aryl iodides. The phosphinite-amine pincer ligands 1-(R2PO)-C6H4-3-(CH2NiPr2) [R2POCNiPr2-H; R = iPr (1a), R = tBu (1b)] and corresponding palladium complexes {2-(R2PO)-C6H3-6-(CH2NiPr2)}PdCl [(R2POCNiPr2)PdCl; R = iPr (2a), R = tBu (2b)] were synthesized in good yields. Treatment of palladium complex 2a with KI and AgOAc afforded the complexes (iPr2POCNiPr2)PdI (3a) and (iPr2POCNiPr2)Pd(OAc) (4a), respectively. Similarly, the reaction of 2a with benzothiazolyl-lithium produces the (iPr2POCNiPr2)Pd(benzothiazolyl) (5a) complex in a quantitative yield. The pincer palladium complex 2a efficiently catalyzes the C-H bond arylation of benzothiazole, substituted-benzoxazoles and 5-aryl oxazoles with diverse aryl iodides in the presence of CuI as a co-catalyst under mild reaction conditions. This represents the first example of a pincer palladium complex being applied for the direct C-H bond arylation of any heterocycle with low catalyst loading. A preliminary mechanistic investigation reveals that palladium nanoparticles are presumably not the catalytically active form of 2a and supports the direct involvement of the catalyst 2a, with complex 5a being a probable key intermediate in the catalytic reaction. This journal is
- Khake, Shrikant M.,Soni, Vineeta,Gonnade, Rajesh G.,Punji, Benudhar
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p. 16084 - 16096
(2014/12/11)
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- Nitro-methyl redox coupling: Efficient approach to 2-hetarylbenzothiazoles from 2-halonitroarene, methylhetarene, and elemental sulfur
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A simple, straightforward, and atom economic approach to 2-hetarylbenzothiazoles starting from 2-halonitroarene, methylhetarene, and elemental sulfur under mild conditions is described. The method is highlighted by the direct redox nitro-methyl reaction for carbon-nitrogen bond formation without an added oxidizing or reducing agent.
- Nguyen, Thanh Binh,Ermolenko, Ludmila,Al-Mourabit, Ali
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supporting information
p. 4218 - 4221
(2013/09/12)
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