Streaming potential measurements 1. Properties of the electrical double layer from crushed rock samples

The ξ potential has been inferred from streaming potential measurements with crushed rock samples as a function of pH and electrolyte concentration for various salts. The value obtained for crushed Fontainebleau sandstone at pH = 5.7 and a KCl solution with a resistivity of 400 Ω m is −40 ± 5 mV, where the error is dominated by sample to sample variations. The sensitivity of the ξ potential to the electrolyte resistivity for KCl is given experimentally by ρ_f^(0.23±0.014) where ρ_f is the electrolyte resistivity. The point of zero charge (pzc) is observed for pH = 2.5 ± 0.1, and the ξ potential is positive for pH pzc. For pH > 5 the variations of the ξ potential with pH can be approximated by ξ(pH)/ξ(5.7) = 1 + (0.068 ± 0.004)(pH - 5.7) for ρ_f = 100 Ω m. The ξ potential has been observed to be sensitive to the valence of the ions and is approximately reduced by the charge of the cation, unless specific adsorption takes place like in the case of Al^3+. The experimental results are well accounted for by a three-layer numerical model of the electrical double layer, and the parameters of this model can be evaluated from the experimental data. The sensitivity of the ξ potential to the rock minerals has also been studied. The ξ potential obtained for granitic rocks is comparable to that obtained for Fontainebleau sandstone but can be reduced by a factor of 2–4 for sandstones containing significant fractions of carbonates or clay. To take into account the effect of the chemical composition of the electrolyte, a chemical efficiency is defined as the ratio of the ξ potential to the ξ potential measured for KCl. This chemical efficiency is measured to be ∼80% for typical groundwater but can be as low as 40% for a water with a high dissolved carbonate content. The set of empirical laws derived from our measurements can be used to assess the magnitude of the streaming potentials expected in natural geophysical systems

Streaming potential during drainage and imbibition

TOTAL are thanked for partially funding Jackson under the TOTAL Chairs programme at Imperial College London and for funding Vinogradov. Shell are thanked for funding Leinov. The Department of Earth Science and Engineering at Imperial College London are thanked for supporting Zhang with a Janet Watson Scholarship. Damien Jougnot, Frederic Perrier and an anonymous reviewer are thanked for their careful and thorough reviews. The data for this paper are available in supporting information or by contacting the corresponding author [email protected] reviewedPublisher PD

Etude experimentale des potentiels electriques spontanes generes lors d'un transfert de fluide biphasique en milieu poreux. Applications en volcanologie

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 81910 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Design, synthesis and biological evaluation of new ansamacrolides for the treatment of bacterial infections

L'antibiorésistance est un problème de santé publique majeur à l'heure actuelle et ceci sera d'autant plus vrai dans les prochaines décennies. Parmi les bactéries impliquées dans ce phénomène alarmant, Acinetobacter baumannii et Mycobacterium abscessus ont développé toutes deux des résistantes à de nombreux antibiotiques actuellement disponibles sur le marché. La recherche et le développement de nouveaux antibiotiques est donc nécessaire afin de lutter contre ces pathogènes.La rifabutine, un macrocycle hémisynthétique de la classe des rifamycines, a récemment montré des activités intéressantes in vitro contre A. baumannii et M. abscessus, ce qui s'est traduit ensuite par une efficacité in vivo de la molécule. La rifabutine semble donc prometteuse dans la lutte contre ces bactéries, cependant l'emploi de cet antibiotique est à ce jour limité. Afin de traiter une infection causée par A. baumannii, la rifabutine doit être injectée par voie intraveineuse, ce qui n'est pas chose simple au vue de la faible solubilité aqueuse de la molécule. Concernant la lutte contre M. abscessus, la rifabutine, bien qu'efficace in vivo, présente une activité limitée contre cette mycobactérie, ce qui peut conduire à un échappement thérapeutique.Les travaux présentés dans ce manuscrit de thèse cherchent donc à pallier les limitations de la rifabutine mentionnées ci-dessus.Dans une première partie, des prodrogues hydrosolubles de la rifabutine ont été synthétisées dans le but de permettre une administration par voie intraveineuse et ainsi de lutter efficacement contre des infections à A. baumannii en clinique. Afin de conduire à la libération de rifabutine après clivage enzymatique dans le plasma, une stratégie de cyclisation intramoléculaire a été employée. Après l'évaluation des composés lors de tests de stabilité plasmatique, des études de relations structure-stabilité ont été réalisées, menant à l'identification de trois prodrogues prometteuses. Des études in vitro supplémentaires ont ensuite été conduites telles que la mesure de la solubilité aqueuse et de l'inhibition de la croissance bactérienne, puis une étude in vivo de pharmacocinétique a finalement été réalisée afin d'identifier un candidat pour le développement.Dans une seconde partie, des analogues de la rifabutine modifiée en position C25 ont été synthétisés afin d'identifier des composés plus puissants. En se basant sur une stratégie de chimie en parallèle, un grand nombre de dérivés a pu rapidement être obtenu, puis ceux-ci ont été évalués contre M. abscessus dans le but de mener des études de relations structure-activité.Antimicrobial resistance is a major public health issue nowadays and this will be even more true in the coming decades. Among the bacteria involved in this alarming phenomenon, Acinetobacter baumannii and Mycobacterium abscessus are both resistant to many antibiotics currently available on the market. Research and development of new antibiotics is therefore necessary to fight these pathogens.Rifabutin, a semi-synthetic macrocyle of the rifamycin class, has recently shown interesting in vitro activities against A. baumannii and M. abscessus, which then translated into in vivo efficacy. Rifabutin therefore seems to be promising to the fight against these bacteria, but the use of this antibiotic is currently limited. In order to treat an infection caused by A. baumannii, rifabutin requires to be injected by intravenous route, which is not so easy because of the low water solubility of the molecule. Concerning the treatment of M. abscessus infections, rifabutin, although effective in vivo, has moderate activity against this mycobacterium, which could lead to therapeutic escape.Therefore, the work presented in this thesis manuscript seeks to address the limitations of rifabutin mentioned above.In a first part, water-soluble prodrugs of rifabutin have been synthesized in order to allow an intravenous injection and thus fight effectively against A. baumannii infections. To achieve the release of rifabutin after enzymatic cleavage in plasma, an intramolecular cyclization strategy was employed. After evaluation of the compounds in plasma stability assays, structure-stability relationship studies were performed, leading to the identification of three promising prodrugs. Additional in vitro studies were then conducted such as the measurement of aqueous solubility and bacterial growth inhibition, and finally an in vivo pharmacokinetic study was performed to be able to select for a preclinical candidate.In a second part, analogues of rifabutin modified at the C25 position were synthesized to identify more potent compounds. Based on a parallel chemistry strategy, a large number of derivatives were rapidly obtained and then evaluated against M. abscessus in order to conduct structure-activity relationship studies

On the Hunt for Next-Generation Antimicrobial Agents: An Online Symposium Organized Jointly by the French Society for Medicinal Chemistry (Société de Chimie Thérapeutique) and the French Microbiology Society (Société Française de Microbiologie) on 9–10 December 2021

The restrictions posed by the COVID-19 pandemic obliged the French Society for Medicinal Chemistry (Société de chimie thérapeutique) and the French Microbiology Society (Société Française de Microbiologie) to organize their joint autumn symposium (entitled “On the hunt for next-generation antimicrobial agents”) online on 9–10 December 2021. The meeting attracted more than 200 researchers from France and abroad with interests in drug discovery, antimicrobial resistance, medicinal chemistry, and related disciplines. This review summarizes the 13 invited keynote lectures. The symposium generated high-level scientific dialogue on the most recent advances in combating antimicrobial resistance. The University of Lille, the Institut Pasteur de Lille, the journal Pharmaceuticals, Oxeltis, and INCATE, sponsored the event