Antioxidant activity of novel indole derivatives and protection of the myocardial damage in rabbits

Novel indole derivatives containing a triazole moiety (1a-d, 2a-c) were synthesized as lead compounds with interesting pharmacological profiles. Their antioxidant activity was investigated on in vitro non-enzymatic rat hepatic microsomal lipid peroxidation. All compounds showed significant effect in the above assay. The effect depended mainly on the attachment position of the triazole moiety on the indole nucleus. The most potent antioxidant derivatives la, 1c and 1d were tested for their protective ability against the oxidative damage of the myocardium after ischemia-reperfusion, in male rabbits which were subjected to 30 min regional ischemia followed by reperfusion. The tested antioxidant compounds 1a, 1c and 1d were continuously infused for 30 min starting at 10th min of ischemia and lasted at 10th min of reperfusion. The concentration of malondialdehyde (MDA, a marker of lipid peroxidation) and hemodynamic parameters (blood pressure and heart rate) were measured in the baseline, at 20th min of the sustained ischemia, 1st and 20th min of reperfusion. It was found that the examined compounds la, 1c and 1d reduced significantly the level of MDA in rabbits under ischemia-reperfusion and proved to be promising substances for further evaluation of anti-ischemic properties.     

The importance of ground-state vibronic mixing in molecular Raman scattering

We consider Albrecht's theory for Raman scattering of fundamentals in the far and pre-resonance regions. Destructive interferences inherent to the A and B terms augment the conventionally suppressed C term dramatically. Raman excitation profiles for the ν₁(a_1g) and ν₆(e_2g fundamentals in benzene can be well fitted with theoretical C-term profiles involving the ¹E_1u(π-π^*) state at 1800 A.     

Heterogeneous activation of oxone using Co3O4

This study explores the potential of heterogeneous activation of Oxone (peroxymonosulfate) in water using cobalt oxides. Two commercially available cobalt oxides, CoO and Co3O4 (CoO.Co2O3) were tested for the activation of peroxymonosulfate and the consequent oxidation of 2,4-dichlorophenol (2,4-DCP) via a sulfate radical mechanism. Both systems, CoO/Oxone and Co3O4/Oxone, were tested at acidic and neutral pH and compared with the homogeneous Co(NO3)2/Oxone. The activity of these systems was evaluated on the basis of the induced transformation of 2,4-DCP as well as the dissolution of cobalt occurred after 2 h of reaction. It was observed that only Co3O4 activates peroxymonosulfate heterogeneously, with its heterogeneity being more pronounced at neutral pH. Both CoO and Co2O3 contained in Co3O4 might be responsible for the observed heterogeneity, and the relative mechanisms are further discussed here. To our knowledge, this is perhaps the first study that documents the heterogeneous activation of peroxymonosulfate with cobalt, the best-known catalyst-activator for this inorganic peroxide.     

Structural basis for recognition of bacterial cell wall teichoic acid by pseudo-symmetric SH3b-like repeats of a viral peptidoglycan hydrolase

Endolysins are bacteriophage-encoded peptidoglycan hydrolases targeting the cell wall of host bacteria via their cell wall-binding domains (CBDs). The molecular basis for selective recognition of surface carbohydrate ligands by CBDs remains elusive. Here, we describe, in atomic detail, the interaction between the Listeria phage endolysin domain CBD500 and its cell wall teichoic acid (WTA) ligands. We show that 3′O-acetylated GlcNAc residues integrated into the WTA polymer chain are the key epitope recognized by a CBD binding cavity located at the interface of tandem copies of beta-barrel, pseudo-symmetric SH3b-like repeats. This cavity consists of multiple aromatic residues making extensive interactions with two GlcNAc acetyl groups via hydrogen bonds and van der Waals contacts, while permitting the docking of the diastereomorphic ligands. Our multidisciplinary approach tackled an extremely challenging protein–glycopolymer complex and delineated a previously unknown recognition mechanism by which a phage endolysin specifically recognizes and targets WTA, suggesting an adaptable model for regulation of endolysin specificity.

Combining genetic, biochemical and computational approaches, we elucidated the molecular mechanisms underlying the recognition of Listeria wall teichoic acid by bacteriophage-encoded SH3b repeats.     

Rapid synthesis of pomalidomide-conjugates for the development of protein degrader libraries

Current methods for the preparation of heterobifunctional pomalidomide-conjugates rely on methods that are often low yielding and produce intractable byproducts. Herein we describe our strategy for the reliable and succinct preparation of pomalidomide-linkers which is essential to the formation of these conjugates. We present the preparation of 18 pomalidomide-linkers in high yield compared to current literature methods. Our findings show that secondary amines consistently afford greater yields than their primary counterparts, a trend that we were able to exploit in the synthesis of several new pomalidomide homo-dimers in enhanced yields compared to similar literature syntheses. This trend was further utilised to develop the first one-pot synthesis of JQ1-pomalidomide conjugates in yields up to 62%, providing a method that is suited to rapid preparation of conjugate libraries as is frequently required for the development of new protein degraders.

Current methods for the preparation of heterobifunctional pomalidomide-conjugates rely on methods that are often low yielding and produce intractable byproducts. Herein we describe our strategy for the succinct preparation of pomalidomide-linkers.     

ZIF-8 degrades in cell media,serum, and some—but not all—common laboratory buffers

ABSTRACT

Drug delivery using metal-organic frameworks (MOF) has elicited interest in their biocompatibility; however, few studies have been conducted on their stability in common buffers, cell media, and blood proteins. In particular, the use of ZIF-8, a MOF interconnected by Zn and methylimidazole, has been frequently employed. In this study, we tested single crystals of ZIF-8 with common laboratory buffers, cell media, and serum, and noted several issues. Buffers containing phosphate and bicarbonate alter the appearance and composition of ZIF-8; however, these buffers do not appear to cause cargo to leak out even when the ZIF-8 itself is displaced by phosphates. On the other hand, serum dissolves ZIF-8, causing premature cargo release. Our results show that ZIF-8 undergoes surface chemistry changes that may affect the interpretation of cellular uptake and cargo release data. On the other hand, it provides a rational explanation as to how ZIF-8 neatly dissolves in vivo.     

Appointment-driven queueing systems with non-punctual customers

Queueing Systems - We consider a single-server queueing system where a finite number of customers arrive over time to receive service. Arrivals are driven by appointments, with a scheduled...     

q-polymatroids and their relation to rank-metric codes

Journal of Algebraic Combinatorics - It is well known that linear rank-metric codes give rise to q-polymatroids. Analogously to matroid theory, one may ask whether a given q-polymatroid is...     

The finite sample properties of sparse M-estimators with pseudo-observations

Annals of the Institute of Statistical Mathematics - We provide finite sample properties of general regularized statistical criteria in the presence of pseudo-observations. Under the restricted...