Influence of an Alkoxy Group on Bis-Triazinyl-Pyridines for Selective Extraction of Americium(III)

The extraction of americium(III), curium(III), and lanthanides(III) from nitric acid by 2,6-bis-(5,6-dimethyl-[1,2,4]-triazin-3-yl)-pyridine and 2,6-bis-(5,6-dimethyl-[1,2,4]-triazin-3-yl)-4-methoxypyridine was studied. The physico-chemical properties of these ligands, such as the protonation and complexation constants, were also determined to describe the influence of different substituent groups. The selectivity of substituted-BTP was confirmed both in complexation and in solvent extraction experiments. The presence of an alkoxy-group in position 4 of the pyridine decreases the BTP selectivity. Influence of a long alkyl chain on protonation and complexation constants was also studied with 2,6-bis-(5,6-dimethyl-[1,2,4]-triazin-3-yl)-4-dodecyloxypyridine.     

Exploring the Interplay Between Ligand Derivatisation and Cation Type in the Assembly of Hybrid Polyoxometalate Mn‐Andersons

Herein a library of hybrid Mn‐Anderson polyoxometalates anions are presented: 1 , [(MnMo₆O₁₈)((OCH₂)₃‐C‐(CH₂)₇CHCH₂)₂]^3?; compound 2 , [(MnMo₆O₁₈)((OCH₂)₃C‐NHCH₂C₁₆H₉)₂]^3?; compound 3 , [(MnMo₆O₁₈)((OCH₂)₃C‐(CH₂)₇CHCH₂)₁((OCH₂)₃C‐NHCH₂C₁₆H₉)₁]^3?; compound 4 , [(MnMo₆O₁₈)((OCH₂)₃C‐NHC(O)CH₂CHCH₂)₂]^3? and compounds 5 – 9 , [(MnMo₆O₁₈)((OCH₂)₃C‐NHC(O)(CH₂)_xCH₃)₂]), where x = 4, 10, 12, 14, and 18 respectively. The compounds resulting from the cation exchange of the anions 1 – 9 to give TBA ( a ) and DMDOA ( b ) salts, and additionally for compounds 1 , 2 and 3 , tetraphenylphosphonium (PPh₄) ( c ) salts, are explored at the air/water interface using scanning force microscopy, showing a range of architectures including hexagonal structures, nanofibers and other supramolecular forms. Additionally the solid‐state structures for compounds 1c , 2c , 4a , 6a , 9a , are presented for the first time and these investigations demonstrate the delicate interplay between the structure of the covalently derivatised hybrid organo‐clusters as well as the ion‐exchange cation types.     

Biomaterial surface properties modulate in vitro rat calvaria osteoblasts response: Roughness and or chemistry?

The aim of this study was a better understanding of the regulation mechanisms of in vitro osteoblast activity on biomaterials. Rat osteoblast behaviour on different surfaces was studied. Surfaces with different roughness (and a similar surface chemistry) or with different surface chemistry (and a similar roughness) were compared. Cellular morphology was observed by scanning electron microscopy and cell adhesion was quantified using an image analysis system. Osteoblast proliferation was quantified by a MTT test and total protein content and alkaline phosphatase (ALP) activity were evaluated by spectrophotometry. Data were compared by statistical analysis.

Results showed that NiTi surface roughness did not influence osteoblasts morphology, adhesion, total protein content and ALP activity whereas it modulated cell proliferation. Roughness was shown to stimulate cell proliferation. For smooth surfaces exhibiting two different chemical compositions, adhesion rate was found to be higher on Thermanox® than on NiTi whereas proliferation was shown to be smaller. ALP activity was also modulated by surface chemistry. Thus, cell adhesion and ALP activity were found to be more governed by surface chemistry than by roughness whereas cell proliferation was shown to be modulated by roughness (this effect increasing during cell culture) and by chemistry (this effect remaining stable in time) together. Total protein content and cell morphology were found to be independent of both parameters (roughness and chemistry). Effects of surface chemistry were discussed in terms of wettability and electron acceptor/donor properties of the surfaces of interest. Immunofluorescence images of adhesion proteins could not demonstrate differences between the three surfaces.     

Methinylogation Approach in Chiral Pharmacophore Design: from Alkynyl‐ to Allenyl‐carbinol Warheads against Tumor Cells

Extension of a structure–activity relationship study of the antitumor cytotoxicity of lipidic dialkynylcarbinols (DACs) is envisaged by formal methinylogation of one of the ethyndiyl moieties of the DAC warhead into the corresponding allenylalkynylcarbinol (AllAC) counterpart. External AllACs were directly obtained by methinylation of the parent DACs with formaldehyde in either the racemic or scalemic series. Isomers containing external progargyl and propynyl motifs were also prepared. Internal AllACs were obtained as racemic statistical mixtures of stereoisomers in two steps from the key C₅‐DAC rac‐TIPS‐C≡C‐CH(OH)‐C≡CH and aldehydes. Kinetic resolution of the (S)‐C₅‐DAC in 97 % ee and (R)‐C₅‐DAC in 99 % ee was achieved by sequential lipase‐mediated acetylation/hydrolysis using the Candida antartica lipase (Novozyme 435). The four internal AllAC stereoisomers were prepared by asymmetric methinylation with (R)‐ or (S)‐diphenylprolinol as chiral auxiliary. Cytotoxicity assays on HCT116 cancer cells showed that the most active (eutomeric) external or internal AllAC exhibits an S configuration, a fatty chain length of n=12, and a 50 % inhibitory concentration IC₅₀≈1.0 μm .     

Effects of the Methanol Extract of Basella alba L (Basellaceae) on Steroid Production in Leydig Cells

In this study, Leydig cells were purified from 70 day-old Sprague Dawley male rats and incubated with 10 and 100 μg/mL of methanol extract of Basella alba (MEBa) for 4 hours followed by the evaluation of cell viability, steroid (testosterone and estradiol) production, and the level of aromatase mRNA. Results showed that MEBa did not affect Leydig cell viability. At the concentration of 10 μg/mL, MEBa significantly stimulated testosterone and estradiol production (p < 0.01 and p < 0.03, respectively), and enhanced aromatase mRNA level (p < 0.04). These observations suggest that MEBa directly stimulated testosterone, estradiol and aromatase mRNA levels in isolated Leydig cells.     

Flavin Conjugates for Delivery of Peptide Nucleic Acids

Oligonucleotides and their analogues, such as peptide nucleic acids (PNAs), can be used in chemical strategies to artificially control gene expression. Inefficient cellular uptake and inappropriate cellular localization still remain obstacles in biological applications, however, especially for PNAs. Here we demonstrate that conjugation of PNAs to flavin resulted in efficient internalization into cells through an endocytic pathway. The flavin–PNAs exhibited antisense activity in the sub‐micromolar range, in the context of a treatment facilitating endosomal escape. Increased endosomal release of flavin conjugates into the cytoplasm and/or nucleus was shown by chloroquine treatment and also—when the flavin–PNA was conjugated to rhodamine, a mild photosensitizer—upon light irradiation. In conclusion, an isoalloxazine moiety can be used as a carrier and attached to a cargo biomolecule, here a PNA, for internalization and functional cytoplasmic/nuclear delivery. Our findings could be useful for further design of PNAs and other oligonucleotide analogues as potent antisense agents.