Critical epinucleation on reconstructured surfaces and first-principle calculation of homonucleation on Si(100)

We introduce the concept of "critical epinucleation to distinguish nucleation on surfaces with and without reconstruction. On a reconstructed surface, the critical classical nucleus is stable against dissociation, but may not yet break the underlying surface reconstruction. Consequently, there must exist a "critical epinucleus" that is not only stable but also has established the epiconfiguration by unreconstructing the underlying substrate. We illustrate this concept by first-principle calculation of homonucleation on reconstructed Si(001) surface where the critical epinucleus consists of six adatoms.     

Photoinduced anti-markovnikov addition of methanol to alkylindenes

Irradiation of acidic methanol solutions of several alkylindenes leads to anti-Markovnikov addition of the solvent to the double bond with previously reported photoisomerizations virtually eliminated.     

Optimal buffer allocation in tandems of last come first served queues

A large fixed number of buffer spaces is given. We consider the problem of allocating these spaces among the nodes of a tandem of last-come-first-served queues with general service time distributions and Poisson external arrivals so as to optimize some performance criterion associated with the time to buffer overflow, such as maximizing its mean or maximizing the probability that it exceeds some value. Consider the following rule of thumb: allocate the buffer spaces in inverse proportion to the logarithms of the effective service rates at the nodes. Here effective service rate denotes the ratio of the service rate to the stationary arrival rate. We prove that this rule of thumb achieves a nearly optimal buffer allocation under the assumption that the service time distributions satisfy an exponential tail condition. This problem has been studied earlier in the context of Jackson networks, where it was shown that the same rule of thumb achieves an allocation that is close to optimal. The technique of proof here is similar, but there are important differences. Both Jackson networks and the LCFS tandems considered here are product form networks (with infinite buffers). Optimism should lead us to expect that the near optimality of this rule of thumb holds much more generally for product-form networks, but this remains a conjecture at present.Research supported by NSF under NCR 8857731, by AT&T, and by Bellcore Inc.Research supported by IBM under a graduate fellowship.     

A novel mixed valence iodide bridged Te(II)-Te(IV) complex featuring diisopropyldithiocarbamate(L) and iodide: ILTeII(I)TeIVL2I

The title compound is a novel mixed ligand and mixed valence complex of tellurium, the crystal structure of which is reported here. The compound crystallizes in the orthorhombic space group, Pca2₁ with four molecules per unit cell, the dimensions of which area=15.209(1),b=20.159(2),c=12.453(1) Å. The structure was solved by the heavy-atom method and refined by fullmatrix least-squares method to a finalR=0.046 andR _w=0.046 for 3011 unique reflections. The structure could be considered as 11 adduct of Te^IVL₂I₂ and Te^IILI (L=diisopropyldithiocarbamate). The two tellurium atoms, Te^II[Te(1)] and Te^IV[Te(2)] display entirely different coordinations and are bridged through iodine I(1) in a symmetrical manner. There is a short Te(1)Te(2) contact distance of 3.542(1) Å.     

Dinuclear rectangular-shaped assemblies of bis-benzimidazolydine salt coordinated to Ag(I) and Cu(I) <Emphasis Type="Italic">N</Emphasis>-heterocyclic carbene complexes and their biological applications

A benzimidazolydine-based novel ligand L2 was prepared from 1,2-bis(benzimidazol-1-yl)ethane (L1) and synthesis of metallocycle complexes such as Ag(I)–N-Heterocyclic Carbene abbreviated as Ag–NHC and Cu(I)–N-Heterocyclic Carbene complex as Cu–NHC were synthesized and then estimated for antimicrobial and antioxidant properties. Synthesis of Ag–NHC and Cu–NHC metallocycle complexes was described. The benzimidazolydine ligand precursor and its Ag–NHC and Cu–NHC were successfully characterized by FT-IR, FT-Raman, 1D and 2D NMR, HR-ESI mass spectra, and cyclic voltammetric studies. In the present work, antimicrobial study discloses that ligand (L1 and L2) do not show inhibitory activity against various pathogens; however, it was gradually increased, when they were coordinated to metals like Ag and Cu. Among the four compounds, the Ag–NHC strongly hampers the growth of fungal strains. The minimal inhibitory concentration (MIC) ranged between 46 and 750 μg mL^?1. A distinctive cell growth reduction was observed in C. albicans when treated with minimum concentration of Ag–NHC complex. Ag–NHC exhibited the ability to prevent the growth of C. albicans by causing severe membrane damage and accumulation of intracellular reactive oxygen species (ROS), which were revealed by fluorescence spectroscopic studies. The tested (L1, L2, Ag–NHC and Cu–NHC) compounds demonstrated significant activity with IC₅₀ values range (0.20–30 μM) for DPPH, OH and NO antioxidant activity. Ascorbic acid was used as standard drug. The radical scavenging potencies of the compounds were explored by employing DPPH, OH and NO assays, in which Ag–NHC exhibited highest inhibitory effect on the radicals [IC₅₀?=?57.3 μM (DPPH), 57.7 μM (OH), 52.3 μM (NO)].     

Iminium ion-enamine cascade reaction enables the asymmetric total syntheses of aspidosperma alkaloids vincadifformine and ervinceine

Asymmetric total synthesis of (+)-vincadifformine and (+)-ervinceine is reported by utilizing an iminium ion triggered cascade reaction using chiral 3,3-disubstituted piperidine imine and 2,3-disubstituted indole derivatives coupling partner. In the first generation total synthesis, the pivotal imine is prepared in excellent stereoselectivity but in moderate yield involving a Birch reduction-alkylation strategy. Furthermore, to improve upon the synthesis of the decisive imine, the more practical second generation route is devised through a Johnson-Claisen rearrangement to access chiral 3,3-disubstituted piperidinone in excellent yield and stereoselectivity. Apart from synthesizing (+)-vincadifformine, this strategy is also exploited for the first asymmetric total synthesis of (+)-ervinceine employing an iminium ion mediated cascade reaction. This distinctive strategy simultaneously sets up two new rings, two new stereogenic centers, and three new sigma bonds in a single operation.     

Targeted Degradation of Transcription Coactivator SRC‐1 through the N‐Degron Pathway

Aberrantly elevated steroid receptor coactivator‐1 (SRC‐1) expression and activity are strongly correlated with cancer progression and metastasis. Here we report, for the first time, the development of a proteolysis targeting chimera (PROTAC) that is composed of a selective SRC‐1 binder linked to a specific ligand for UBR box, a unique class of E3 ligases recognizing N‐degrons. We showed that the bifunctional molecule efficiently and selectively induced the degradation of SRC‐1 in cells through the N‐degron pathway. Importantly, given the ubiquitous expression of the UBR protein in most cells, PROTACs targeting the UBR box could degrade a protein of interest regardless of cell types. We also showed that the SRC‐1 degrader significantly suppressed cancer cell invasion and migration in vitro and in vivo. Together, these results demonstrate that the SRC‐1 degrader can be an invaluable chemical tool in the studies of SRC‐1 functions. Moreover, our findings suggest PROTACs based on the N‐degron pathway as a widely useful strategy to degrade disease‐relevant proteins.