Sugar-based low-molecular-weight gelators are an interesting new class of compounds that are important in supramolecular chemistry and for the preparation of advanced materials. Previously, we synthesized a series of ester and carbamate derivatives of 4,6-O-benzylidene methyl-alpha-D-glucopyranoside and found that monosubstituted alkynyl esters with five to seven carbons and monosubstituted carbamates with saturated five- and seven-carbon chains are good gelators. To understand the structural requirement for the gelation of the carbamate derivatives (O-linked carbamates), a diverse series of analogs, including alkynyl, aryl, and alkyl halide derivatives, were prepared and analyzed. We found that for gelation the O-linked carbamate derivatives have different structural preferences than the ester derivatives. To exhibit gellation, the ester analogs favor alkyl-containing terminal acetylene groups and the carbamoyl derivatives prefer saturated hydrocarbons. Both the esters and the carbamates showed good gelation properties when they were functionalized with aryl side chains. We also synthesized and screened a new series of carbamates (N-linked carbamates) in which the nitrogen atom of the carbamate group is directly attached to the sugar ring. The N-linked carbamates are good gelators for aqueous DMSO and ethanol solutions, and two of the compounds are also able to form gels in pure water. Optical microscopy and scanning electron microscopy were used to characterize several representative gels. In general, long, narrow, uniform fibrous networks were observed for effective gelators. The structure-gelation correlation obtained here can be used in the design of new sugar-based low-molecular-weight gelators.

No abstract

A general, efficient, and highly diastereoselective method for the synthesis of structurally and sterically diverse P-chiral phosphine oxides was developed. The method relies on sequential nucleophilic substitution on the versatile chiral phosphinyl transfer agent 1,3,2-benzoxazaphosphinine-2-oxide, which features enhanced and differentiated P-N and P-O bond reactivity toward nucleophiles. The reactivities of both bonds are fine-tuned to allow cleavage to occur even with sterically hindered nucleophiles under mild conditions.

Cytochrome P450 enzymes (CYPs) are important phase I enzymes involved in the metabolism of endogenous and xenobiotic compounds mainly through mono-oxygenation reactions into more polar and easier to excrete species. In addition to their role in detoxification, they play important roles in the biosynthesis of endogenous compounds and the bioactivation of xenobiotics. Coumarins, phytochemicals abundant in food and commonly used in fragrances and cosmetics, have been shown to interact with P450 enzymes as substrates and/or inhibitors. In this review, these interactions and their significance in pharmacology and toxicology are discussed in detail.

The cytochrome P450 (CYP) family 1A enzymes, CYP1A1 and CYP1A2, are two of the most important enzymes implicated in the metabolism of endogenous and exogenous compounds through oxidation. These enzymes are also known to metabolize environmental procarcinogens into carcinogenic species, leading to the advent of several types of cancer. The development of selective inhibitors for these P450 enzymes, mitigating procarcinogenic oxidative effects, has been the focus of many studies in recent years. CYP1A1 is mainly found in extrahepatic tissues while CYP1A2 is the major CYP enzyme in human liver. Many molecules have been found to be metabolized by both of these enzymes, with varying rates and/or positions of oxidation. A complete understanding of the factors that govern the specificity and potency for the two CYP 1A enzymes is critical to the development of effective inhibitors. Computational molecular modeling tools have been used by several research groups to decipher the specificity and potency factors of the CYP1A1 and CYP1A2 substrates. In this review, we perform a thorough analysis of the computational studies that are ligand-based and protein-ligand complex-based to catalog the various factors that govern the specificity/potency toward these two enzymes.

Diacetylene-containing glycolipids are a unique class of compounds that are able to self-assemble and form ordered supramolecular structures. Polymerizable diacetylene glycolipids that can function as low molecular weight gelators are particularly interesting molecules which can lead to stimuli-responsive smart materials. To discover efficient organogelators with built-in functionality that may be useful in sensing local environmental changes, we have synthesized a series of novel diacetylene-containing amide and urea derivatives using D-glucosamine as the starting material. Both amphiphilic and dipolar glycolipids were synthesized, and these compounds are effective gelators for several organic solvents and aqueous solutions. The resulting gels can be cross-linked under 6 W UV light to produce blue or purple polydiacetylene gels. The cross-linked gels obtained from urea derivatives are generally dark blue and exhibit blue to red color transitions upon heating. Compared to the urea derivatives, the analogous diacetylene amides produced blue to deep purple polymerized gels, depending on the structures of the gelators. The morphologies of the gels were characterized by optical microscopy and scanning electron microscopy. Typically, self-assembled fibrous networks were observed. The synthesis and characterization of these polymerizable gelators and their UV-vis absorption upon polymerization are reported.

In humans, cytochrome P450 1A2 is the major enzyme metabolizing environmental arylamines or heterocyclic amines into carcinogens. Since evidence shows that planar triangle-shaped molecules are capable of selectively inhibiting P450 1A2, 16 triangular flavone, and coumarin derivatives were designed and synthesized for these studies. Among these compounds, 7,8-furanoflavone time-dependently inhibits P450 1A2 with a KI value of 0.44 μM. With a 5 min preincubation in the presence of NADPH, 0.01 μM 7,8-furanoflavone completely inactivates P450 1A2 but does not influence the activities of P450s 1A1 and 1B1. Another target compound, 7,8-pyrano-4-trifluoromethylcoumarin, is found to be a competitive inhibitor, showing high selectivity for the inhibition of P450 1A2 with a Ki of 0.39 μM, 155- and 52-fold lower than its Ki values against P450s 1A1 and 1B1, respectively. In yeast AhR activation assays, 7,8-pyrano-4-trifluoromethylcoumarin does not activate aryl hydrocarbon receptor when the concentration is lower than 1 μM, suggesting that this compound would not up-regulate AhR-caused P450 enzyme expression. In-cell P450 1A2 inhibition assays show that 7,8-pyrano-4-trifluoromethylcoumarin decreases the MROD activity in HepG2 cells at concentrations higher than 1 μM. Thus, using 7,8-pyrano-4-trifluoromethylcoumarin, a selective and specific P450 1A2 action suppression could be achieved, indicating the potential for the development of P450 1A2-targeting cancer preventive agents.

SummarySmall molecular gelators are a class of compounds with potential applications for soft biomaterials. Low molecular weight hydrogelators are especially useful for exploring biomedical applications. Previously, we found that 4,6-O-benzylidene acetal protected D-glucose and D-glucosamine are well-suited as building blocks for the construction of low molecular weight gelators. To better understand the scope of D-glucosamine derivatives as gelators, we synthesized and screened a novel class of N-acetylglucosamine derivatives with a p-methoxybenzylidene acetal protective group. This modification did not exert a negative influence on the gelation. On the contrary, it actually enhanced the gelation tendency for many derivatives. The introduction of the additional methoxy group on the phenyl ring led to low molecular weight gelators with a higher pH responsiveness. The resulting gels were stable at neutral pH values but degraded in an acidic environment. The release profiles of naproxen from the pH responsive gels were also analyzed under acidic and neutral conditions. Our findings are useful for the design of novel triggered release self-assembling systems and can provide an insight into the influence of the the structure on gelation.