Molecular Dynamic and Docking Simulation to Prevent Thymine Dimer as the Main Reason for Skin Cancer

Two major types can be repaired UV-induced DNA lesions. The first one is a light-dependent process that reverts UV damage applying particular wavelengths. The second is a light-independent process that excises the light-damaged region under novo synthesis of an intact DNA. The iGEMDOCK has been used for this study, and the acceptable thymine dimer can be defined for the binding site in whole DNA structures. The DNA is worked with two thymine in a segment of nucleic acids, and iGEMDOCK can help to prepare a suitable binding between them. The total energies of the model systems are a total of several partial energies as follows: E(system) = E(bond) + E(angle) + E(torsion) +E(over) +E(vdW) + E(Coulomb) + E(Specific). EvdW +E(Coulomb) represents the dispersive and electrostatic energies contribution between all atoms, respectively. Finally, E(Specific) is system-specific energy such as lone-pair, conjugation, and hydrogen binding. The DFT and HF calculations of the thymine dimer exhibited that the ring fusion at the C5 and C6 atoms of two thymine bases produced a four-member cyclo-butane puckered ring, as well as the feature, is seen with the MPn or Moller-Pleset level. In addition, the UV radiations between 360 nm to 200 nm have been investigated for the study of thymine dimers.

Impact of The Arylation of N-Bridged Annulated BODIPY Dyes In Photophysical Properties

Functionalization of BODIPY dyes is commonly used to modulate photophysical properties. Among the chemical modification of these dyes, ring fusion indifferent faces of dipyrromethene cores is gaining attention in the literature, due to the modulation ofemission/absorption properties and fluorophores with increased bright. N-bridged annulated BODIPYs were recently synthesized and shows intense bright and blu shifted emission. However, few examples of substituted compounds are described and none involving arylation with extention of the p-conjugation. In this manuscript, it is shown an optimized method for the synthesis of N-bridged annulated BODIPYs, including arylated derivatives, and the studies of molecular properties. It is also shown that fluorinated aryl substituted N-bridged annulated BODIPYs show high quantum yields and are red-shifted compared to unsubstituted examples. The work open opportunities for application of the new developed compounds as probes.

Truxene Functionalized Star-Shaped Non-fullerene Acceptor With Selenium-Annulated Perylene Diimides for Efficient Organic Solar Cells

An electron acceptor with a truxene core and ring-fusion perylene diimide (PDI) tripolymer annulated by selenium (Se) branch, named as FTr-3PDI-Se, is designed and synthesized. FTr-3PDI-Se exhibits large conjugated planar conformation, strong absorption spectra in the regions of 300–400 and 450–550 nm, the deep HOMO energy level of 6.10 eV, and high decomposition temperature above 400°C. The FTr-3PDI-Se: PBDB-T-2Cl based device achieved a disappointing power conversion efficiency (PCE) of 1.6% together with a high Voc of 1.12 V. The low PCE was due to the large aggregates of blend film, the imbalanced hole/electron transport and low PL quenching efficiencies. The high Voc can be attributed to the high-lying LUMO level of FTr-3PDI-Se and the low-lying HOMO level of PBDB-T-2Cl. Our research presents an interesting and effective molecule-designing method to develop non-fullerene acceptor.

Hyperglycemia-Induced Dysregulated Fusion Intermediates in Insulin-Secreting Cells Visualized by Super-Resolution Microscopy

Impaired insulin release is a hallmark of type 2 diabetes and is closely related to chronically elevated glucose concentrations, known as “glucotoxicity.” However, the molecular mechanisms by which glucotoxicity impairs insulin secretion remain poorly understood. In addition to known kiss-and-run and kiss-and-stay fusion events in INS-1 cells, ultrafast Hessian structured illumination microscopy (Hessian SIM) enables full fusion to be categorized according to the newly identified structures, such as ring fusion (those with enlarged pores) or dot fusion (those without apparent pores). In addition, we identified four fusion intermediates during insulin exocytosis: initial pore opening, vesicle collapse, enlarged pore formation, and final pore dilation. Long-term incubation in supraphysiological doses of glucose reduced exocytosis in general and increased the occurrence of kiss-and-run events at the expense of reduced full fusion. In addition, hyperglycemia delayed pore opening, vesicle collapse, and enlarged pore formation in full fusion events. It also reduced the size of apparently enlarged pores, all of which contributed to the compromised insulin secretion. These phenotypes were mostly due to the hyperglycemia-induced reduction in syntaxin-1A (Stx-1A) and SNAP-25 protein, since they could be recapitulated by the knockdown of endogenous Stx-1A and SNAP-25. These findings suggest essential roles for the vesicle fusion type and intermediates in regulating insulin secretion from pancreatic beta cells in normal and disease conditions.

Practical Synthesis of Iboxamycin, a Potent Antibiotic Candidate, in Amounts Suitable for Studies in Animal Infection Models

A gram-scale synthesis of iboxamycin, an antibiotic candidate bearing a fused bicyclic amino acid residue, is presented. A pivotal transformation in the route involves an intramolecular hydrosilylation–oxidation sequence to set the ring-fusion stereocenters of the bicyclic scaffold. Other notable features of the synthesis include a high-yielding, highly diastereoselective alkylation of a pseudoephenamine amide, a convergent sp³–sp² Negishi coupling, and a one-pot transacetalization–reduction reaction to form the target compound’s oxepane ring. Implementation of this synthetic strategy has provided ample quantities of iboxamycin to allow for its <i>in vivo</i> profiling in murine models of infection.

Practical Synthesis of Iboxamycin, a Potent Antibiotic Candidate, in Amounts Suitable for Studies in Animal Infection Models

A gram-scale synthesis of iboxamycin, an antibiotic candidate bearing a fused bicyclic amino acid residue, is presented. A pivotal transformation in the route involves an intramolecular hydrosilylation–oxidation sequence to set the ring-fusion stereocenters of the bicyclic scaffold. Other notable features of the synthesis include a high-yielding, highly diastereoselective alkylation of a pseudoephenamine amide, a convergent sp³–sp² Negishi coupling, and a one-pot transacetalization–reduction reaction to form the target compound’s oxepane ring. Implementation of this synthetic strategy has provided ample quantities of iboxamycin to allow for its <i>in vivo</i> profiling in murine models of infection.

Endo- and exohedral chloro-fulleride as η5 ligands: A DFT study on the first-row transition metal complexes

C60 fullerene coordinates to transition metals in η2-fashion through its C-C bond at [6,6] ring fusion whereas other coordination modes η3, η4, η5 and η6 are rarely observed. The coordination...