Spontaneous formation of a chiral (MoOS)-based cluster driven by dimeric {TeO}-based templates.

Utilization of [Mo2S2O2(H2O)6]2+ and a tellurite anion led to the formation of three new clusters, 1-3, with unique structural features. The tellurite anion not only templated the formation of [(Mo2O2S2)4(TeO3)(OH)9]3-1 and [(Mo2O2S2)12(TeO3)4(TeO4)2 (OH)18]10-3, but also the in situ generation of two different types of dimeric {Te2O6} based moieties induced the spontaneous assembly of the chiral [(Mo2O2S2)10(TeO3)(Te2O6)2(OH)18]8- anionic cluster, 2.

Exploring structural complexity in the discovery and self-assembly of a family of nanoscale chalcoxides from {SeMo} to {SeMo}.

Herein, we show the controlled generation of multi-component libraries based on the [MoSO]/MoO/SeO/CO system leading to the formation of a whole new family of nanosized molecular chalcoxides, {SeMo} 1, {SeMo} 2, {SeMo} 3, {SeMo} 4 and {SeMo} 5, of the general formula {(MoOS)(OH)(SeO)(CO)(MoO)}, where a, b, c, d, e, n = [16, 20, 8, 6, 2, 20] for 1, [18, 24, 8, 6, 2, 20] for 2, [24, 32, 8, 8, 4, 24] for 3, [28, 32, 20, 8, 0, 32] for 4 and [34, 36, 26, 8, 0, 36] for 5. The coordination modulation effect offered by the SeO and the CO anions lead to the generation of new building blocks, [(MoOS)(OH)(CO) (MoO)], and the discovery of a new family of clusters of increasing nuclearity and complexity.

Tellurite-Squarate Driven Assembly of a New Family of Nanoscale Clusters Based on (Mo O S ).

The preparation and characterization of a new family of four polyoxothiometalate (POTM) clusters are reported, with varying size and complexity, based upon the dimeric [Mo O S (H O) ] cation with the general formula (NMe ) K [(Mo O S ) (TeO ) (C O ) (OH) ] where a,b,c,d,e,f={1,7,14,2,4,10}=1, {Mo Te }; {2,26,36,12,10,48}=2, {Mo Te }; {0,11,15,3,3,21}=3, {Mo Te }; {2,6,12,2,4,16}=4, {Mo Te }. The incorporation of tellurite anions allowed the fine tuning of the templating and bridging of the available building blocks, leading to new topologies of increased complexity. The structural diversity of this family of compounds ranges from the highly symmetrical cross-shaped {Mo Te } to the stacked ring structure of {Mo Te }, which is the largest tellurium-containing POTM cluster reported so far.

Time-resolved assembly of cluster-in-cluster {Ag₁₂}-in-{W₇₆} polyoxometalates under supramolecular control.

We report the time-resolved supramolecular assembly of a series of nanoscale polyoxometalate clusters (from the same one-pot reaction) of the form: [H(10+m)Ag18Cl(Te3W38O134)2]n, where n=1 and m=0 for compound 1 (after 4 days), n=2 and m=3 for compound 2 (after 10 days), and n=∞ and m=5 for compound 3 (after 14 days). The reaction is based upon the self-organization of two {Te3W38} units around a single chloride template and the formation of a {Ag12} cluster, giving a {Ag12}-in-{W76} cluster-in-cluster in compound 1, which further aggregates to cluster compounds 2 and 3 by supramolecular Ag-POM interactions. The proposed mechanism for the formation of the clusters has been studied by ESI-MS.

Combinatorial mutagenesis of MBNL1 zinc fingers elucidates distinct classes of regulatory events.

The RNA binding protein and alternative splicing factor Muscleblind-like 1 (MBNL1) has been a topic of intense study due to its role in myotonic dystrophy (DM) pathogenesis. MBNL1 contains four zinc finger (ZF) RNA binding domains arranged in two pairs. Through combinatorial mutagenesis of the ZF domains, we demonstrate that the pairs of ZFs have differential affinity for RNA and subsequently differential splicing activities.

Activation of the p38 pathway by a novel monoketone curcumin analog, EF24, suggests a potential combination strategy.

Increasing attention has been given to the anticancer effects of curcumin and the ability of this natural product to inhibit cancer cell proliferation. New curcumin analogs have been developed to optimize the in vitro and in vivo activity of the parent compound yet retain the same safety profile. EF24, a fluorinated synthetic analog, surpasses curcumin in its ability to inhibit cancer cell viability and down-regulate TNFα-induced NF-κB activation.

MBNL1 binds GC motifs embedded in pyrimidines to regulate alternative splicing.

Muscleblind-like 1 (MBNL1) regulates alternative splicing and is a key player in the disease mechanism of myotonic dystrophy (DM). In DM, MBNL1 becomes sequestered to expanded CUG/CCUG repeat RNAs resulting in splicing defects, which lead to disease symptoms. In order to understand MBNL1's role in both the disease mechanism of DM and alternative splicing regulation, we sought to identify its RNA-binding motif.

Probing the origin of the compromised catalysis of E. coli alkaline phosphatase in its promiscuous sulfatase reaction.

The catalytic promiscuity of E. coli alkaline phosphatase (AP) and many other enzymes provides a unique opportunity to dissect the origin of enzymatic rate enhancements via a comparative approach. Here, we use kinetic isotope effects (KIEs) to explore the origin of the 109-fold greater catalytic proficiency by AP for phosphate monoester hydrolysis relative to sulfate monoester hydrolysis.

The thermodynamics of phosphate versus phosphorothioate ester hydrolysis.

Phosphorothioate esters are phosphate esters in which one of the nonbridging oxygen atoms has been replaced by sulfur. In the comparative hydrolysis reactions of phosphorothioate and phosphate esters, the sulfur substitution accelerates the rates of the monoesters while slowing the rates of diesters and of triesters. Previously measured enthalpies and entropies of activation for the hydrolysis reactions of the monoesters, p-nitrophenyl phosphate and p-nitrophenyl phosphorothioate, were compared to the activation parameters measured herein for the diesters, ethyl p-nitrophenyl phosphate and ethyl p-nitrophenyl phosphorothioate, and the triesters, diethyl p-nitrophenyl phosphate and diethyl p-nitrophenyl phosphorothioate.

A concerted mechanism for the transfer of the thiophosphinoyl group from aryl dimethylphosphinothioate esters to oxyanionic nucleophiles in aqueous solution.

Earlier work on the hydrolysis of aryl phosphinothioate esters has led to contradictory mechanistic conclusions. To resolve this mechanistic ambiguity, we have measured linear free energy relationships (beta(nuc) and beta(lg)) and kinetic isotope effects for the reactions of oxyanions with aryl dimethylphosphinothioates. For the attack of nucleophiles on 4-nitrophenyl dimethylphosphinothioate, beta(nuc) = 0.

Transition state differences in hydrolysis reactions of alkyl versus aryl phosphate monoester monoanions.

Although aryl phosphates have been the subject of numerous experimental studies, far less data bearing on the mechanism and transition states for alkyl phosphate reactions have been presented. Except for esters with very good leaving groups such as 2,4-dinitrophenol, the monoanion of phosphate esters is more reactive than the dianion. Several mechanisms have been proposed for the hydrolysis of the monoanion species.