Electrochemical low valent cobalt-catalyzed addition of aryl and vinyl chlorides to α-ketoamides via C-Cl bond activation.

The development of an electrochemical cobalt catalyzed C-Cl bond activation at room temperature for the nucleophilic addition of aryl and vinyl chlorides to α-ketoamides is described. The overall method operates through an electrochemically induced low valent cobalt catalyst that oxidatively adds to aryl or vinyl chlorides affording medicinally important 3-hydroxy oxindole and 3-hydroxypyrrolidinone scaffolds. The development of an enantioselective version using a chiral pyrox ligand is also demonstrated.

Paired Electrolysis for Decarboxylative Cyanation: 4-CN-Pyridine, a Versatile Nitrile Source.

A decarboxylative cyanation of amino acids under paired electrochemical reaction conditions has been developed. 4-CN-pyridine was found to be a new and effective cyanation reagent under catalyst-free conditions. Mechanistic studies support a nucleophilic reaction pathway, and the cyanation protocol can be applied to diverse substrates including N,N-dialkyl aniline and indole derivatives.

Photoactivatable prodrug for simultaneous release of mertansine and CO along with a BODIPY derivative as a luminescent marker in mitochondria: a proof of concept for NIR image-guided cancer therapy.

Controlled and efficient activation is the crucial aspect of designing an effective prodrug. Herein we demonstrate a proof of concept for a light activatable prodrug with desired organelle specificity. Mertansine, a benzoansamacrolide, is an efficient microtubule-targeting compound that binds at or near the vinblastine-binding site in the mitochondrial region to induce mitotic arrest and cell death through apoptosis. Despite its efficacy even in the nanomolar level, this has failed in stage 2 of human clinical trials owing to the lack of drug specificity and the deleterious systemic toxicity. To get around this problem, a recent trend is to develop an antibody-conjugatable maytansinoid with improved tumor/organelle-specificity and lesser systematic toxicity. Endogenous CO is recognized as a regulator of cellular function and for its obligatory role in cell apoptosis. CO blocks the proliferation of cancer cells and effector T cells, and the primary target is reported to be the mitochondria. We report herein a new mitochondria-specific prodrug conjugate (Pro-DC) that undergoes a photocleavage reaction on irradiation with a 400 nm source (1.0 mW cm-2) to induce a simultaneous release of the therapeutic components mertansine and CO along with a BODIPY derivative (BODIPY(PPH3)2) as a luminescent marker in the mitochondrial matrix. The efficacy of the process is demonstrated using MCF-7 cells and could effectively be visualized by probing the intracellular luminescence of BODIPY(PPH3)2. This provides a proof-of-concept for designing a prodrug for image-guided combination therapy for mainstream treatment of cancer.

Single Center 7 Year Experience of Coronary Artery Perforation: Angiographic and Procedural Characteristics, Management and Outcome.

CONTEXT: Coronary artery perforation is a rare but potentially catastrophic complication of percutaneous coronary intervention (PCI). It is infrequent complication of PCI. AIMS: The objective of the study is to report the 7-year experience of coronary artery perforation with respect to incidence, clinical and angiographic characteristics, management and outcomes. SETTINGS AND DESIGN: The study involved retrospective analysis of single centre 7 years of percutaneous coronary intervention data. Patients who had complication of coronary artery perforation during PCI were identified and included in the study. SUBJECTS AND METHODS: Retrospective analysis of clinical, angiographic and procedural characteristics as well as management and outcome of coronary artery perforation was done. STATISTICAL ANALYSIS USED: The whole data were tabulated, variables were presented as mean and percentages and comparison was done within them. RESULTS: A total of 37 cases of coronary artery perforation were identified from 4532 PCI performed. Most of the coronary artery perforation belonged to Ellis Type II and Type III (both n = 15) followed by Type III CS and Type I. Lesions belonged to AHC/AHA Type C in 31 cases. Most frequent mechanism of coronary artery perforation was related to the use of guidewire and balloon (both n = 17). The total of 8 cases presented with cardiac tamponade requiring pericardiocentesis. Eleven cases required emergency covered stent implantation. In two cases microcoil was used while one case required polyvinyl alcohol particles to seal the perforation site. There was no in-hospital mortality while 30-day mortality occurred in one patient. One case was referred for emergency surgery. CONCLUSIONS: Coronary artery perforation is rare but potentially fatal complication of percutaneous coronary intervention. Complication of coronary artery perforation can be managed effectively in the catheterization laboratory without the need of emergency of bailout surgery and in-hospital outcomes remain good in the majority of cases.