Olefin Metathesis in Continuous Flow Reactor Employing Polar Ruthenium Catalyst and Soluble Metal Scavenger for Instant Purification of Products of Pharmaceutical Interest.

In recent years, the development of continuous-flow reactors has attracted growing attention from the synthetic community. Moreover, findings in the precise control of the reaction parameters and improved mass/heat transfer have made the flow setup an attractive alternative to batch reactors, both in academia and industry, enabling safe and easy scaling-up of synthetic processes. Even though a majority of the pharmaceutical industry currently rely on batch reactors or semibatch reactors, many are integrating flow technology because of easier maintenance and lower risks. Herein, we demonstrate an operationally simple flow setup for homogeneous ring-closing metathesis, which is applicable to the synthesis of active pharmaceutical ingredients precursors or analogues with high efficiency, low residence time, and in a green solvent. Furthermore, through the addition of a soluble metal scavenger in the subsequent step within the flow system, the level of ruthenium contamination in the final product can be greatly reduced (to less than 5 ppm). To ensure that this method is applicable for industrial usage, an upscale process including a 24 h continuous-flow reaction for more than 60 g of a Sildenafil analogue was achieved in a continuous-flow fashion by adjusting the tubing size and flow rate accordingly.

Preliminary evaluation of application of a 3-dimensional network structure of siloxanes Dergall preparation on chick embryo development and microbiological status of eggshells.

The spatial network structure of Dergall is based on substances nontoxic to humans and the environment which, when applied on solid surfaces, creates a coating that reduces bacterial cell adhesion. The bacteriostatic properties of siloxanes are based on a purely physical action mechanism which excludes development of drug-resistant microorganisms. The aims of the present study were to 1) evaluate a Dergall layer formed on the eggshell surface regarding the potential harmful effects on the chick embryo; 2) evaluate antimicrobial activity and estimate the prolongation time of Dergall's potential antimicrobial activity. Dergall at a concentration of 0.6% formed a layer on the eggshell surface. In vitro testing of the potential harmful effects of Dergall by means of a hen embryo test of the chorioallantoic membrane showed no irritation reaction at a concentration of 3% and lower. The hatchability of the groups sprayed with a Dergall water solution with a concentration of 0 to 5% was 89.1 to 93.8% for fertilized eggs (P > 0.05) but decreased to 63.7% (P < 0.05) in the group sprayed with a 6% concentration of the solution. This phenomenon was caused by embryo mortality in the first week of incubation. At the concentration of 0.6%, Dergall exhibited strong antibacterial properties against bacteria such as Staphylococcus aureus, Escherichia coli, Shigella dysenteriae, Shigella flexneri, and Salmonella typhimurium. For Streptococcus pyogenes, the highest antibacterial activity of Dergall was reported in the concentrations of 100 and 50%. For Pseudomonas aeruginosa, no antibacterial activity of Dergall was generally observed, but in vivo testing showed a strong decrease of all gram-negative bacteria growth. Moreover, a prolonged antimicrobial effect lasting until 3 D after disinfection was observed, which makes Dergall a safe and efficient disinfectant.

Reduced graphene oxide doping with nanometer-sized ferrocene moieties - New active material for glucose redox sensors.

Herein, we present that the reduced graphene oxide (rGO) doped with nanometer-sized ferrocene moieties is a new, excellent active material for redox sensors. Two distinct approaches were utilized for the modification of rGO. The first method was based on the covalent decoration of rGO via the addition of azomethine ylide generated from the ferrocenecarboxaldehyde oxime. The second approach utilized the adsorption of 1,1'-ferrocenedicarboxylic acid on the graphene sheet via the π-π stacking. The morphology of the synthesized graphene materials was studied by application of microscopic techniques, whereas the Raman data allowed the characteristics of the tested materials in terms of their structural properties. The tested graphene materials doped with ferrocene moieties were used as a bioactive platform for glucose oxidase (GOx) immobilization. The enzyme was immobilized onto the rGO materials in two ways: (i) using a crosslinking agent - glutaraldehyde (GA) and (ii) by formation of the amide bonds between carboxylic groups of rGO-Fc(COOH)2 and amine groups from enzyme. Ferrocene moieties present at the graphene surface play the role of mediator in the electron transfer between the redox center of GOx and the electrode surface. The functionality of the constructed biosensors has been tested on real samples. The results of the recovery rates showed a satisfying degree of accuracy toward determination of glucose concentration. Examination of the potential interfering species has demonstrated favorable sensitivity and selectivity of the designed biosensor for the detection of glucose.