Biotransformation of Cortisone with Rhodococcus rhodnii: Synthesis of New Steroids

Cortisone is a steroid widely used as an anti-inflammatory drug able to suppress the immune system, thus reducing inflammation and attendant pain and swelling at the site of an injury. Due to its numerous side effects, especially in prolonged and high-dose therapies, the development of the pharmaceutical industry is currently aimed at finding new compounds with similar activities but with minor or no side effects. Biotransformations are an important methodology towards more sustainable industrial processes, according to the principles of “green chemistry”. In this work, the biotransformation of cortisone with Rhodococcus rhodnii DSM 43960 to give two new steroids, i.e., 1,9β,17,21-tetrahydoxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11,20-dione and 1,9β,17,20β,21-pentahydoxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11-one, is reported. These new steroids have been fully characterized.     

Formation of C(sp2)?Boronate Esters by Borylative Cyclization of Alkynes Using BCl3

BCl₃ is an inexpensive electrophile which induces the borylative cyclization of a wide range of substituted alkynes to regioselectively form polycycles containing synthetically versatile C(sp²) boronate esters. It proceeds rapidly, with good yields and is compatible with a range of functional groups and substitution patterns. Intermolecular 1,2‐carboboration of alkynes is also achieved using BCl₃ to generate trisubstituted vinyl boronate esters.     

Medium-high resolution electrochemical genotyping of HLA-DQ2/DQ8 for detection of predisposition to coeliac disease

Coeliac disease is a small intestinal disorder, induced by ingestion of gluten in genetically predisposed individuals. Coeliac disease has been strongly linked to human leukocyte antigens (HLA) located on chromosome 6, with almost 100 % of coeliac disease sufferers carrying either a HLA-DQ2 or HLA-DQ8 heterodimer, with the majority carrying HLA-DQ2 encoded by the DQA1*05:01/05:05, DQB1*02:01/02:02 alleles, whereas the remaining carry the HLA-DQ8 encoded by the DQA1*03:01, DQB1*03:02 alleles. In this work, we present the development of a multiplex electrochemical genosensor array of 36 electrodes, housed within a dedicated microfluidic platform and using a total of 10 sequence-specific probes for rapid medium-high resolution HLA-DQ2/DQ8 genotyping. An evaluation of the selectivity of the designed probes was carried out with the target sequences and 44 potentially interfering alleles, including single base mismatch differentiations; good selectivity was demonstrated. The performance of the electrochemical genosensor array was validated, analyzing real human samples for the presence of HLA-DQ2/DQ8 alleles, and compared with those obtained using laboratory-based HLA typing, and an excellent correlation was obtained.

Conformational Changes in Calcium‐Sensor Proteins under Molecular Crowding Conditions

Fundamental components of signaling pathways are switch modes in key proteins that control start, duration, and ending of diverse signal transduction events. A large group of switch proteins are Ca²⁺ sensors, which undergo conformational changes in response to oscillating intracellular Ca²⁺ concentrations. Here we use dynamic light scattering and a recently developed approach based on surface plasmon resonance to compare the protein dynamics of a diverse set of prototypical Ca²⁺‐binding proteins including calmodulin, troponin C, recoverin, and guanylate cyclase‐activating protein. Surface plasmon resonance biosensor technology allows monitoring conformational changes under molecular crowding conditions, yielding for each Ca²⁺‐sensor protein a fingerprint profile that reflects different hydrodynamic properties under changing Ca²⁺ conditions and is extremely sensitive to even fine alterations induced by point mutations. We see, for example, a correlation between surface plasmon resonance, dynamic light scattering, and size‐exclusion chromatography data. Thus, changes in protein conformation correlate not only with the hydrodynamic size, but also with a rearrangement of the protein hydration shell and a change of the dielectric constant of water or of the protein–water interface. Our study provides insight into how rather small signaling proteins that have very similar three‐dimensional folding patterns differ in their Ca²⁺‐occupied functional state under crowding conditions.     

Different approaches to the study of chelating agents for iron and aluminium overload pathologies

Our objective is to illustrate the activity of the groups operating in Italy involved in identification and study of new chelating agents, mainly intended for treatment of human pathology correlated with metal overload. The objective of “chelation therapy” is removal of toxic metal ions from the human body or attenuation of their toxicity by transforming them into less toxic compounds or by dislocating them from the site at which they exert a toxic action. Because most of this research activity is related to chelating agents for iron and aluminium, diseases related to these two metal ions are briefly treated. Iron overload is the most common metal toxicity disease worldwide. The toxicity of aluminium in dialysis patients was a serious problem for haemodialysis units in the seventies and eighties of the last century. In particular, this review focuses on research performed by the group at Cagliari and Ferrara, and by that at Padova. The former is studying, above all, bisphosphonate and kojic acid derivatives, and the latter is investigating 3,4-hydroxypyridinecarboxylic acids with differently substituted pyridinic rings.

Exafs studies of LiYF 4 -LiREF 4 solid solutions

In this work we are investigating dopant environments in LiYF 4 -LiREF 4 (RE=rare-earth cations) solid solutions, via EXAFS. The main aims are to identify the local environmental symmetry and the average lattice distortion as a function of the concentration and the type of the RE ion. LiY 1 m x RE x F 4 (RE=Gd or Lu) (0< x <1) single crystals were grown by the Czochralski technique under argon or CF 4 atmosphere, crystal-pulling rates were 0.6-1 v mm/h for <100>-oriented boules, with 8-25 v rpm rotation rates. Most of the crystals were also codoped with 2.7 v mol% of neodymium in the melt. EXAFS measurements were performed in transmission and fluorescence modes in the synchrotron XAS line of the LNLS, Campinas, Brazil, in and above the L III absorption edges of the RE ions. The samples were prepared as powder films, for the transmission mode measurements, and as powder or single crystals for fluorescence mode measurements. The WINXAS program was used for data reduction and fitting, and the FEFF6 package was used for the simulations of the spectra. The EXAFS oscillation curves were obtained by standard procedure.     

Computer modelling of intrinsic defects and migration processes in KY3F10

Abstract

The computer modelling technique was used in the present work to study the intrinsic defects and the migration processes in KY₃F₁₀. The main intrinsic disorder was found to be F Frenkel pairs but at higher temperatures it is possible that KF pseudo-Schottky defects could also be present in the material. The ionic conduction process is mainly due to the fluorine ions migrating via both vacancy and interstitialcy mechanisms.