Photochemical synthesis of a “cage” compound in a microreactor: Rigorous comparison with a batch photoreactor

An intramolecular [2 + 2] photocycloaddition is performed in a microphotoreactor (0.81 mL) built by winding FEP tubing around a commercially available Pyrex immersion well in which a medium pressure mercury lamp is inserted. A rigorous comparison with a batch photoreactor (225 mL) is proposed by means of a simple model coupling the reaction kinetics with the mass, momentum and radiative transfer equations. This serves as a basis to explain why the chemical conversion and the irradiation time are respectively increased and reduced in the microphotoreactor relative to those in the batch photoreactor. Through this simple model reaction, some criteria for transposing photochemical synthesis from a batch photoreactor to a continuous microphotoreactor are defined

La micro-échelle en synthèse organique : un outil commun chimie/génie chimique

Cet article est une restitution courte de la présentation réalisée au cours des JIREC 2013 sur l’enseignement de la notion de changement d’échelle et de passage d’un mode batch à un mode continu en synthèse organique. L’enjeu est de faire travailler des étudiants issus des départements chimie et génie chimique autour d’un même outil, le microréacteur. Au cours d’une séance de travaux pratiques, les étudiants mettent en oeuvre une synthèse organique en continu à micro-échelle et comparent les résultats obtenus à ceux du procédé batch. Ils appréhendent ainsi la notion de synthèse en continu et de suivi cinétique le long du microréacteur et comprennent l’intérêt et les difficultés liés à la petite échelle. L’outil microréacteur mis en place à l’INP-ENSIACET peut être transféré vers d’autres formations de type ingénieurs, mais aussi CPGE, BTS ou IUT, pour accompagner le lien entre les domaines « génie de la réaction » et « synthèse organique »

Prediction of the general transcription factors associated with RNA polymerase II in Plasmodium falciparum: conserved features and differences relative to other eukaryotes

BACKGROUND: To date, only a few transcription factors have been identified in the genome of the parasite Plasmodium falciparum, the causative agent of malaria. Moreover, no detailed molecular analysis of its basal transcription machinery, which is otherwise well-conserved in the crown group of eukaryotes, has yet been reported. In this study, we have used a combination of sensitive sequence analysis methods to predict the existence of several parasite encoded general transcription factors associated with RNA polymerase II. RESULTS: Several orthologs of general transcription factors associated with RNA polymerase II can be predicted among the hypothetical proteins of the P. falciparum genome using the two-dimensional Hydrophobic Cluster Analysis (HCA) together with profile-based search methods (PSI-BLAST). These predicted orthologous genes encoding putative transcription factors include the large subunit of TFIIA and two candidates for its small subunit, the TFIIE β-subunit, which would associate with the previously known TFIIE α-subunit, the TFIIF β-subunit, as well as the p62/TFB1 subunit of the TFIIH core. Within TFIID, the putative orthologs of TAF1, TAF2, TAF7 and TAF10 were also predicted. However, no candidates for TAFs with classical histone fold domain (HFD) were found, suggesting an unusual architecture of TFIID complex of RNA polymerase II in the parasite. CONCLUSION: Taken together, these results suggest that more general transcription factors may be present in the P. falciparum proteome than initially thought. The prediction of these orthologous general transcription factors opens the way for further studies dealing with transcriptional regulation in P. falciparum. These alternative and sensitive sequence analysis methods can help to identify candidates for other transcriptional regulatory factors in P. falciparum. They will also facilitate the prediction of biological functions for several orphan proteins from other apicomplexan parasites such as Toxoplasma gondii, Cryptosporidium parvum and Eimeria

Stoichio-kinetic model discrimination and parameter identification in continuous microreactors

Kinetics is essential for chemical reactor modelling, in particular to reduce the inherent risks of extrapolation going along with scaling-up. Pharmaceutical industries are especially concerned. However, when chemical systems are very complex, development of good models may lead to prohibitively expensive and time consuming experiments. The aim of this paper is to describe an efficient experimental design strategy for discrimination of stoichio-kinetic models. The proposed methodology is based on model-based experimental design(optimal design), which uses information already acquired on models to determine the best conditions to implement a new experiment with the highest discrimination potential. The combination with microreactor technology is also proposed in this work. The whole procedure for model discrimination is firstly described in detail and then, applied to a numerical study case, consisting of a chemical synthesis carried out in a microreactor. The discrimination procedure efficiently leads to the determination of the single adequate model among the various potential models proposed before the implementation of the designed experiments.It is verified that the procedure does not depend on the set of preliminary experiments and is time-saving when compared to a classical factorial plan

Microreactors as a Tool for Acquiring Kinetic Data on Photochemical Reactions

For the first time, the application of microreactors as a tool for acquiring kinetic data on a photochemical reaction is demonstrated. For illustration, a T-photochromic system is considered. By using modeling tools and carrying out specific experiments in a spiral-shaped microreactor irradiated by an ultraviolet/light-emitting diode (UV-LED) array, the two kinetic parameters of the reaction, namely, quantum yield and rate of thermal back reaction, are determined. Once these parameters are known, the photochromic reaction is performed in two other microreactors in order to investigate a wider range of operating conditions. It is observed that a critical residence time exists beyond which the conversion into the open form decreases due to a decomposition reaction. The value of the critical residence depends on the microreactor type, which can be predicted by applying the model developed

Effects of Process Parameters on an Inverse Concentrated Miniemulsion Flowing in a Microchannel

Emulsions are of great industrial interest due to their wide variety and end‐use properties. Microfluidics systems provide excellent control of transport phenomena. Hence, the influence of operating parameters on a concentrated inverse miniemulsion flowing in a microfluidic system was investigated. The feasibility of maintaining the emulsion in a microfluidic device was clearly demonstrated and the associated operating domain identified. Due to its influence on rheology, the effect of temperature on the droplet size distribution was quantified. Under specific conditions, a mass transfer phenomenon between the train of water drops and the smallest droplets of the emulsion was found, potentially explained by a difference in osmotic pressure between the two aqueous phases

Flow photochemistry: a meso-scale reactor for industrial applications

Developing flow photochemistry, especially at meso-scale where significant productivity is required, remains challenging. There is a need for innovative equipments generating highly controlled flow under light irradiation. In this work, a commercial solution, developed by Corning, is presented and studied by LGC and MEPI on an intramolecular (2+2) photo-cycloaddition. Detailed experimental and modelling analysis has been performed to emphasize the flow reactor behaviour and performances, and demonstrate its capability in producing up to 30g.h-1 of the desired molecule. Through this simple model reaction, the G1 photo-reactor is shown to be an efficient meso-scale reactor for industrial photo-applications development and production

Biological brain age prediction using machine learning on structural neuroimaging data: Multi-cohort validation against biomarkers of Alzheimer's disease and neurodegeneration stratified by sex

Brain-age can be inferred from structural neuroimaging and compared to chronological age (brain-age delta) as a marker of biological brain aging. Accelerated aging has been found in neurodegenerative disorders like Alzheimer's disease (AD), but its validation against markers of neurodegeneration and AD is lacking. Here, imaging-derived measures from the UK Biobank dataset (N=22,661) were used to predict brain-age in 2,314 cognitively unimpaired (CU) individuals at higher risk of AD and mild cognitive impaired (MCI) patients from four independent cohorts with available biomarker data: ALFA+, ADNI, EPAD, and OASIS. Brain-age delta was associated with abnormal amyloid-β, more advanced stages (AT) of AD pathology and APOE-ε4 status. Brain-age delta was positively associated with plasma neurofilament light, a marker of neurodegeneration, and sex differences in the brain effects of this marker were found. These results validate brain-age delta as a non-invasive marker of biological brain aging in non-demented individuals with abnormal levels of biomarkers of AD and axonal injury