The Power of Kinetic Inertness in Improving Platinum Anticancer Therapy by Circumventing Resistance and Ameliorating Nephrotoxicity

Even in the modern era of precision medicine and immunotherapy, chemotherapy with platinum (Pt) drugs remains among the most commonly prescribed medications against a variety of cancers. Unfortunately, the broad applicability of these blockbuster Pt drugs is severely limited by intrinsic and/or acquired resistance, and high systemic toxicity. Considering the strong interconnection between kinetic lability and undesired shortcomings of clinical Pt drugs, we rationally designed kinetically inert organometallic Pt based anticancer agents with a novel mechanism of action. Using a combination of in vitro and in vivo assays, we demonstrated that the development of a remarkably efficacious but kinetically inert Pt anticancer agent is feasible. Along with exerting promising antitumor efficacy in Pt-sensitive as well as Pt-resistant tumors in vivo, our best candidate has the ability to mitigate the nephrotoxicity issue associated with cisplatin. In addition to demonstrating, for the first time, the power of kinetic inertness in improving the therapeutic benefits of Pt based anticancer therapy, we describe the detailed mechanism of action of our best kinetically inert antitumor agent. This study will certainly pave the way for designing the next generation of anticancer drugs for effective treatment of various cancers.     

Two new mononuclear cobalt(II) complexes of pyrazole-based ligands: synthesis,structures and magnetic studies

We have synthesized two mononuclear cobalt(II) complexes (1 and 2) of pyrazole-based bidentate (NN) and tridentate (NNN) tripodal ligands. X-ray crystal structure determination reveals that complex 1 has a tetrahedral geometry, while complex 2 has a trigonal–bipyramidal geometry. Both the complexes have been characterized by variable-temperature magnetic measurements between 2 and 300 K. A weak ferromagnetic exchange interaction (J = +1.5 cm^?1) is observed for complex 2. Due to the presence of supramolecular CH···Cl and π···π interactions, a good magnetostructural correlation was found between the D parameter and angular distortion (δ) for complex 1 and related complexes reported in the literature.     

Cp*CoIII‐Catalyzed C(sp3)−H Bond Amidation of 8‐Methylquinoline

An efficient and external oxidant‐free, Cp*Co^III‐catalyzed C(sp³)?H bond amidation of 8‐methylquinoline, using oxazolone as an efficient amidating agent, is reported for the first time under mild conditions. The reaction is selective and tolerates a variety of functional groups. Based on previous reports and experimental results, the deprotonation pathway proceeds through an external base‐assisted concerted metalation and deprotonation process.     

Fashionable Co-operative Sensing of Bivalent Zn2+ and Cd2+ in Attendance of OAc− by Use of Simple Sensor: Exploration of Molecular Logic Gate and Docking Studies

Journal of Fluorescence - The Schiff-base probe H2VL [6,6'-((1E,1'E)-hydrazine-1,2 diylidenebis(methanylylidene))bis(2-methoxyphenol)] is synthesized and structurally characterized by...     

On single courier problem

A new set of NP problems defined as Courier Problems that is motivated from the requirements in railway wagon scheduling is proposed. The general version includes many mobile couriers. The simplest version of this will consider a single courier. An algorithm to transform the single courier problem into a traveling salesman problem is presented.     

Synthesis of Some 9-Aryl-9-Aza-2,8-Dioxo-4,5-Benzo-Bicyclo [4.3.0] Nonane,A New Keterocyclic System

A new and versatile synthetic procedure for the title compound is reported. Two routes for the cyclisation of diazoketones (4) have been developed.     

Quantum mechanics of rapidly and periodically driven systems

This review deals with the dynamics of quantum systems that are subject to high frequency external perturbations. Though the problem may look hopelessly time-dependent, and poised on the extreme opposite side of adiabaticity, there exists a ‘Kapitza Window’ over which the dynamics can be treated in terms of effective time-independent Hamiltonians. The consequent results are important in the context of atomic traps as well as quantum optic properties of atoms in intense and high-frequency electromagnetic fields.      

A highly selective and sensitive in vivo fluorosensor for zinc(II) without cytotoxicity

A highly selective and sensitive fluorescent Zn(2+) sensor, 2,6-bis(2-hydroxy-benzoic acid hydrazide)-4-methylphenol (1), was designed and synthesized. In aqueous THF (4 : 6 v/v) ligand 1 induces a 2 : 1 complex formation with respect to Zn(2+) at physiological pH. This probe features visible light excitation(390 nm) and emission (490 nm) profiles, excellent selectivity responses for Zn(2+)over other competing biological metal ions with K(d) < 1 pM(2), LOD < 1 ng L(-1) and about 680 fold enhancement in fluorescent intensity upon Zn(2+) binding. It also exhibits cell permeability and intracellular Zn(2+) sensing in A375 human melanoma cancer cell.     

Role of environment and confinement in quantum dissipative dynamics: A pedestrian approach

In this paper, the long time and short time behavior of a free quantum Brownian particle and of a quantum harmonic oscillator coupled to a quantum heat bath is investigated for different spectral density functions. Not only are the usual Ohmic, Drude or radiation heat bath schemes employed to derive explicit expressions for the generalized susceptibility χ(t)$\chi \left(t\right)$ and the position correlation function σ(t)$\sigma \left(t\right)$ but also the most intriguing frequency dependent heat bath spectra are considered. Emphasis is laid on the dependence on the low-frequency behavior but in some cases also the high-frequency cutoff becomes relevant. The present investigation also sheds light on the role of boundary in long time and short time behavior of quantum dissipative systems.     

Surfactant-induced modulation of fluorosensor activity: a simple way to maximize the sensor efficiency

Tuning of the sensory capability of a potentially bioactive indoloquinolizine system, namely, 3-acetyl-4-oxo-6,7-dihydro-12H-indolo-[2,3-a]-quinolizine (AODIQ), is described in a biomimicking micellar nanocage. It has been shown that surfactant concentration dictates the sensing behavior of the fluorophore toward physiologically essential trace metals, such as Cu2+. This is a simple, efficient, and general technique that allows one to utilize the sensor to its maximum efficiency.