Synthesis,Structure, and Optical Studies of Donor–Acceptor‐Type Near‐Infrared (NIR) Aza–Boron‐Dipyrromethene (BODIPY) Dyes

Six donor–acceptor‐type near‐infrared (NIR) aza–boron‐dipyrromethene (BODIPY) dyes and their corresponding aza–dipyrrins were designed and synthesized. The donor moieties at the 1,7‐positions of the aza–BODIPY core were varied from naphthyl to N‐phenylcarbazole to N‐butylcarbazole. The 3,5‐positions were also substituted with phenyl or thienyl groups in the aza–BODIPYs. Photophysical, electrochemical, and computational studies were carried out. The absorption and emission spectra of aza–BODIPYs were significantly redshifted (≈100 nm) relative to the parent tetraphenylaza–BODIPY. Fluorescence studies suggested effective energy transfer (up to 93 %) from donor groups to the aza–BODIPY core in all of the compounds under study. Time‐dependent (TD)‐DFT studies indicated effective electronic interactions between energy donor groups and aza–dipyrrin unit in all the aza–BODIPYs studied. The HOMO–LUMO gap (ΔE) calculated from cyclic voltammetry data was found to be lower for six aza–BODIPYs relative to their corresponding aza–dipyrrins.     

Quality improvement in wellness reports in patients with Crohn’s disease

Quality-of-life tests are used because they provide information about symptoms, potential complications, and response to treatment with patients as active participants. We took Crohn’s disease (CD) during diet supplement with omega 3 or 6 fatty acids (ω-3FA vs. ω-6FA) Impact^® as an example and assessed three quality-of-life tests: The inflammatory bowel disease questionnaire (IBDQ), the Beck depression inventory (BDI), and the visual analogue scale (VAS). These tests have been found inconvenient, not informative in daily clinical use, and inhomogeneous in international studies.We used the body mass index (BMI) (kg/m²) as a clinical quantitative effect parameter and the patient self-rated quality of life as qualitative variables during recovery. All ratings were converted into numeric standardized percent point before isolation of optimized ratings.BMI increased on average 2 BMI units in both diet groups. The classical wellness tests or their traditional sub-scores identified improved outcome during recovery, primarily in the ω-3FA group. Separate items on bowel function, wellness, and asthenia possessed the best item responsiveness – (30–35 percent point). A new selective scale with the six most responsive items is proposed as a specific optimized questionnaire.Based on CD as an example, we described a method to isolate responsive items from quality-of-life tests and described a method to optimize their sensitivity. We propose for validation a new optimized disease – specific VAS scale for rating of wellness during treatment in inflammatory bowel disease, in which ω-3FA seemed superior in improving outcome.Presented at the 10th Conference Quality in the Spotlight, March 2005, Antwerp, Belgium.     

Stereocontrolled synthesis of methyl silanediol peptide mimics

The treatment of chiral sulfinimines with (methyldiphenylsilyl)lithium gives alpha-(methyldiphenylsilyl)sulfinamides with excellent diastereoselectivity, and in good yield. The presence of alpha-protons on the imines is also well tolerated. The sulfinamide auxiliary is easily removed via treatment with methanolic HCl and the resulting amine extended into peptide chains accordingly. The diphenylsilyl moiety is a resilient protecting group for the corresponding silanediol, which can be unmasked via treatment with TfOH, followed by aqueous hydrolysis. The crude silanediol may be isolated and purified as its corresponding bis-TMS siloxane via protection with TMSCl, and converted back to the desired silanediol via hydrolysis with aqueous KOH. Efforts to apply this approach to biologically relevant silanediol peptide mimics, with a view to protease inhibition, are described.     

Titelbild: Enantiospecific C?H Activation Using Ruthenium Nanocatalysts (Angew. Chem. 36/2015)

The activation of C H bonds has revolutionized modern synthetic chemistry. However, no general strategy for enantiospecific C H activation has been developed to date. We herein report an enantiospecific C H activation reaction followed by deuterium incorporation at stereogenic centers. Mechanistic studies suggest that the selectivity for the α‐position of the directing heteroatom results from a four‐membered dimetallacycle as the key intermediate. This work paves the way to novel molecular chemistry on nanoparticles.     

Heteroleptic transition metal complexes of Schiff‐base‐derived ligands exert their antifungal activity by disrupting membrane integrity

Development of new treatment strategies and chemotherapeutic agents is urgently needed to combat the growing multidrug resistant species of Candida. In this direction, a new series of Cu (II), Co (II), Ni (II) and Zn (II) heteroleptic complexes were synthesized, characterized and evaluated for antifungal activity. Based on spectral characterization and physical measurements, an octahedral geometry was assigned to [Co(L1)(L2)ClH₂O] ( C2 ), [Ni(L1)(L2)ClH₂O] ( C3 ), [Zn(L1)(L2)ClH₂O] ( C4 ) complexes, while a distorted octahedral geometry was assigned to [Cu(L1)(L2)ClH₂O] ( C1 ) complex. All the synthesized compounds were tested for antifungal activity against 11 Candida albicans isolates, including fluconazole (FLC)‐resistant isolates, by determining minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC), following CLSI guidelines. The mechanism of their antifungal activity was assessed by studying their effect on the plasma membrane using flow cytometry and quantifying the ergosterol contents. All the test compounds showed varying levels of antifungal activity. Both the ligands showed moderate antifungal activity with a median MIC value of 100 μg/mL with no fungicidal activity. Compound C3 was the most potent compound with median MIC and MFC values of 0.10 and 1.60 μg/mL, respectively. Flow cytometry analysis revealed that these compounds at MFC values disrupt the cell membrane, resulting in propidium iodide entering the cells. These compounds also reduced a considerable amount of ergosterol content after treating the cells with MIC and sub‐MIC values. This study indicates that these compounds have high antifungal activity against C. albicans, and have the potential to be developed as novel antifungal drugs.     

Synthesis,spectral characterization,DFT studies and biological activity of novel Ligand 1‐(2‐cyclohexyl thioethyl) piperidine and its complexes with group 12 metal chlorides

C₆H₁₁S^‐Na⁺ (generated insitu by reaction of NaOH with C₆H₁₁SH) on treatment with 1‐(2‐chloroethyl) piperidine hydrochloride under N₂ atmosphere resulted in (1‐(2‐cyclohexyl thioethyl) piperidine) ( L ¹ ) as orange solid. It's complexes having the formula [ZnCl₂. L¹] ( 1 ), [CdCl₂. (L¹)] ( 2 ) and [HgCl₂. L¹] ( 3 ) have been prepared. L ¹ and its complexes 1‐3 were characterized on the basis of physico‐chemical and spectral (FT‐IR, Mass, ¹H, ¹³C and DEPT 135^o NMR) studies. Powder XRD diffraction pattern reveals the crystalline nature of L¹ and complex 1 . Complexes 1‐3 adopt distorted tetrahedral geometry showing bidentate mode of coordination through S and N. Using DFT‐based optimization of structures, the HOMO‐LUMO energy gaps and molecular electrostatic potential maps (EPM) of compound L¹ and complexes 1‐ 3 were theoretically calculated at the B3LYP/6‐311G (d, p) level of theory. HOMO‐LUMO energy gap was calculated which allowed the calculation of relative properties like chemical hardness, chemical inertness, chemical potential, nucleophilicity and electrophillicity index of the synthesized products. The experimentally obtained IR and NMR results showed a good correlation with those of the theoretical ones. Ligand L ¹ and complexes 1‐3 display significant antibacterial and antifungal activity.     

A general,flexible, ring closing metathesis (RCM) based strategy for accessing the fused furo[3,2-b]furanone moiety present in diverse bioactive natural products

A simple and straightforward methodology of general utility to construct sterically encumbered furo[3,2-b]furanone scaffolds present in a diverse range of bioactive natural products is delineated. The methodology emanates from readily available Morita–Baylis–Hillman adducts and employs sequential ring closing metathesis and oxy-Michael addition cascade as the key steps.     

Site selective [bmIm]OH catalyzed CC bond functionalization under green conditions

Effective methodology that activates selectively either end of a carbon–carbon triple bond requires key challenge of differentiating between the multitude of CC bonds present in complex organic molecule. The synthetic strategy exploited the electronic biases within the substrate and successfully achieved site–selective [bmIm]OH catalyzed CC bond functionalization under mild reaction conditions. This resulted in C-2-selective addition of phenacyl bromide on p-substituted phenyl acetylene and C-1 selective addition on the o-substituted phenyl acetylene leading to CC bond formation. The reaction proceeded smoothly with excellent yield under ambient conditions. This report demonstrates the progress on the catalytic activity of recyclable [bmIm]OH for selective CC bond formation.     

An interference effect in the channel radiative neutron capture process

This study shows that the small thermal neutron radiative capture cross sections in ¹²C and neighbouring nuclides are the result of destructive interference between the potential scattering wave and the resonance scattering wave near the nuclear surface, resulting in a drastic cancellation in the radial integral. The behaviour of the scattering wave function is examined, and the general condition for the occurrence of such cancellation is discussed. The expression for the channel radiative capture cross section which has been derived has the same structure as the Lane-Lynn formula but is expressed in terms of different parameters. In addition, this investigation shows that if the optical model well depth is adjusted so that the binding energy of the $\text{p}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ orbit in ¹²C is kept at the experimental value, then the calculated results for the potential and channel radiative neutron capture cross sections are insensitive to the value of the nuclear radius.     

Single-particle states at very high spin in the light dysprosium isotopes

High-spin states in ^150–152Dy have been investigated. Gamma-gamma coincidences in all three isotopes have been studied with Compton-suppressed Ge(Li) detectors. For ¹⁵¹Dy, lifetimes of the high-spin states have been measured by the recoil-distance technique. The spin and parity assignments, transition rates, and level systematics support the interpretation of the observed states as proton particle-hole excitations coupled to aligned valence neutron configurations. Shell-model calculations, based on effective interactions and a ¹⁴⁶Gd core, quantitatively reproduce the observed level patterns, and the predicted transition rates qualitatively agree with the observed values.