Divergent Chemistry Paths for 3D and 1D Metallo‐Covalent Organic Frameworks (COFs)

The marriage of dynamic covalent chemistry (DCC) and coordination chemistry is a powerful tool for assembling complex architectures from simple building units. Recently, the synthesis of woven covalent organic frameworks (COFs) with topologically fascinating structures has been achieved using this approach. However, the scope is highly limited and there is a need to discover new pathways that can assemble covalently linked organic threads into crystalline frameworks. Herein, we have identified branching pathways leading to the assembly of three‐dimensional (3D) woven COFs or one‐dimensional (1D) metallo‐COFs (mCOFs), where the mechanism is underpinned by the absence or presence of ligand exchange.     

A simple, high yield method for the synthesis of organic wires from aromatic molecules using nitric acid as the solvent

Using concentrated nitric acid as the solvent, and water as the non-solvent, one-dimensional (1D) organic nanowires can be synthesized in a simple, one-pot process with high yield. The method has broad validity to a wide range of aromatic molecules for the synthesis of derivatized organic wires.     

Scaffolding catalysts: highly enantioselective desymmetrization reactions

Ex-changing places: a highly enantioselective desymmetrization of 1,2-diols has been developed in which the catalyst utilizes reversible covalent bonding to the substrate to achieve both high selectivity and rate acceleration (see scheme, PMP=pentalmethylpiperidine, TBS=tert-butyldimethylsilyl). Induced intramolecularity is responsible for the enhanced rate, thus allowing the reaction to be performed at room temperature.     

Enantioselective hydroformylation of aniline derivatives

We have developed a ligand that reversibly binds to aniline substrates, allowing for the control of regioselectivity and enantioselectivity in hydroformylation. In this paper we address how the electronics of the aniline ring affect both the binding of the substrate to the ligand and the enantioselectivity in this reaction.     

Global uniqueness in an inverse problem for time fractional diffusion equations

Given $(M,g)$, a compact connected Riemannian manifold of dimension $d?2$, with boundary ?M, we consider an initial boundary value problem for a fractional diffusion equation on $(0,T)\times M$, $T>0$, with time-fractional Caputo derivative of order $\alpha \in (0,1)\cup (1,2)$. We prove uniqueness in the inverse problem of determining the smooth manifold $(M,g)$ (up to an isometry), and various time-independent smooth coefficients appearing in this equation, from measurements of the solutions on a subset of ?M at fixed time. In the “flat” case where M is a compact subset of ${\mathbb{R}}^d$, two out the three coefficients ρ (density), a (conductivity) and q (potential) appearing in the equation $\rho {?}_t^{\alpha }u?\mathrm{div}\left(a\mathrm{?}u\right)+qu=0$ on $(0,T)\times M$ are recovered simultaneously.     

On a Hardy operator inequality

The famous Hardy inequality asserts that if f is a non-negative p-integrable \((p>1)\) function on \((0,\infty )\), then

$$\begin{aligned} \int _{0}^{\infty }\left( \frac{1}{x}\int _{0}^{x}f(t)dt\right) ^pdx\le \left( \frac{p}{p-1}\right) ^p\int _{0}^{\infty }f(x)^pdx. \end{aligned}$$

We present an external form of the Hardy inequality for Hilbert space operators. Moreover, utilizing the operator log-convex functions, a refinement of the operator Hardy inequality is also given.

     

Molecular dynamics simulations on the inhibition of Cyclin-Dependent Kinases 2 and 5 in the presence of activators

Interests in CDK2 and CDK5 have stemmed mainly from their association with cancer and neuronal migration or differentiation related diseases and the need to design selective inhibitors for these kinases. Molecular dynamics (MD) simulations have not only become a viable approach to drug design because of advances in computer technology but are increasingly an integral part of drug discovery processes. It is common in MD simulations of inhibitor/CDK complexes to exclude the activator of the CDKs in the structural models to keep computational time tractable. In this paper, we present simulation results of CDK2 and CDK5 with roscovitine using models with and without their activators (cyclinA and p25). While p25 was found to induce slight changes in CDK5, the calculations support that cyclinA leads to significant conformational changes near the active site of CDK2. This suggests that detailed and structure-based inhibitor design targeted at these CDKs should employ activator-included models of the kinases. Comparisons between P/CDK2/cyclinA/roscovitine and CDK5/p25/roscovitine complexes reveal differences in the conformations of the glutamine around the active sites, which may be exploited to find highly selective inhibitors with respect to CDK2 and CDK5.     

Melatonin Induces Autophagy via Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress Pathway in Colorectal Cancer Cells

Even though an increasing number of anticancer treatments have been discovered, the mortality rates of colorectal cancer (CRC) have still been high in the past few years. It has been discovered that melatonin has pro-apoptotic properties and counteracts inflammation, proliferation, angiogenesis, cell invasion, and cell migration. In previous studies, melatonin has been shown to have an anticancer effect in multiple tumors, including CRC, but the underlying mechanisms of melatonin action on CRC have not been fully explored. Thus, in this study, we investigated the role of autophagy pathways in CRC cells treated with melatonin. In vitro CRC cell models, HT-29, SW48, and Caco-2, were treated with melatonin. CRC cell death, oxidative stress, and autophagic vacuoles formation were induced by melatonin in a dose-dependent manner. Several autophagy pathways were examined, including the endoplasmic reticulum (ER) stress, 5′–adenosine monophosphate-activated protein kinase (AMPK), phosphoinositide 3-kinase (PI3K), serine/threonine-specific protein kinase (Akt), and mammalian target of rapamycin (mTOR) signaling pathways. Our results showed that melatonin significantly induced autophagy via the ER stress pathway in CRC cells. In conclusion, melatonin demonstrated a potential as an anticancer drug for CRC.     

Intermediacy of an N-heterocyclic carbene complex in the catalytic C-H activation of a substituted benzimidazole

An N-heterocyclic carbene complex was found to be the active catalyst in the Rh(I)-catalyzed intramolecular coupling of an alkenyl group to a C-H bond of a substituted benzimidazole. Kinetic studies demonstrated that the catalytic cyclization is zero-order in substrate and first-order in catalyst. Furthermore, DFT calculations with a model system suggest that the rate-limiting step involves insertion of the alkenyl double bond into the rhodium-carbene bond.