Anion-pi interactions in cyanuric acids: a combined crystallographic and computational study

Several structures of pi complexes of isocyanuric acid and of several thio derivatives with anions have been computed by using high level ab initio calculations. The nature of the complexes has been studied by means of the method of molecular interaction potential with polarization (MIPp) and Bader's theory of atoms-in-molecules. These molecules form favorable complexes with anions and can be used as binding units for building receptors for the molecular recognition of anions. In several cases, the anion-pi interaction has been demonstrated experimentally by means of X-ray crystallography.     

Asymptotic behavior of solutions of variational equations

In questo articolo si considerano equazioni differenziali ordinarie del secondo ordine della forma $$\{ A(u')u'\} ' + \delta (r)A(u')u' + f(r,u) = 0,$$ dove cioè la nonlinearità è presente sia nella variabile soluzioneu che nella sua derivata. Si forniscono proprietà di monotonia, oscillazione e un accurato studio del comportamento asintotico all’ infinito delle soluzioni, quandoA, δ,f hanno crescite asintotiche di tipo algebrico.     

Canonical connections with an algebraic curvature tensor field on naturally reductive spaces

We study Ambrose-Singer connections with an algebraic curvature tensor on simply connected manifolds carrying a homogeneous Riemannian structure of class ₃ in the classification given by F. Tricerri and L. Vanhecke.This work was partially supported by MURST.     

Untersuchungen an Kristallhydraten anorganischer Salze, 8. Mitt. Interpretation der Schwingungsspektren vonM(BF4)2·6H2O fürM=Fe2+, Co2+, Ni2+

The infrared and Raman spectra were recorded in the range 4000–160 cm^–1 forM(BF₄)₂·6 H₂O whereM=Fe²⁺, Co²⁺, Ni²⁺. The spectroscopic data support the X-ray structural data in showing that in the crystal hydrates studied two kinds of hydrogen bonds are present: H₂O...H₂O and OH₂... F₄B^–. The energies and molecular force constants (f _OH and fH₂O) andr _OH for OH₂...F₄B^– were calculated for the three crystal hydrates. It was found that the bond OH₂... F₄B^– is comparatively weak, with mean energy 3.7–3.3 kcal/mol. Two types of water molecule with different structures are existing as the first are participating in H₂O...H–O–H...F₄B^– and the second in BF₄ ^–...H–O–H...F₄B^–.     

Analysis of conformational equilibria in aplidine using selective excitation 2D NMR spectroscopy and molecular mechanics/dynamics calculations

Aplidine (dehydrodidemnin B), a natural product with potent antitumor activity currently in multicenter phase II clinical trials, exists in DMSO as a mixture of four slowly interconverting conformations in a ratio of 47:33:13:7. NMR spectroscopy shows that these arise as a consequence of cis/trans isomerization about the NMe-Leu(7)-Pro(8) and Pro(8)-Pyr amide bonds of the molecule's side chain. Two major conformations account for 47% and 33% of the total population, a ratio of 60:40 between the two. They correspond to the cis- and trans-isomers, respectively, about the Pro(8)-Pyr amide bond. Two minor conformers arise as a consequence of similar isomerism about the Pro(8)-Pyr amide bond, but in structures in which the NMe-Leu(7)-Pro(8) amide bond is cis rather than trans. These account for approximately 13% and 7% of the total population, corresponding to a ratio of 65:35 cis/trans, respectively. Molecular dynamics simulations show that the three-dimensional structures of all four conformational isomers are similar in the macrocycle and that all are essentially unchanged with respect to the macrocycle of didemnin B. Significant differences in the conformation of the molecule's side chain are, however, observed between major and minor pairs. Analysis of hydrogen-bonding patterns shows that each major conformer exhibits a beta-turn like structure and is stabilized by hydrogen bonding between a different carbonyl group of the pyruvyl unit of the molecule's side chain and the NH of the Thr(6) residue. The minor isomers have a cis-amide bond between the NMe-Leu(7) and Pro(8) residues that obliges the side chain to adopt an extended disposition where hydrogen bonding to the macrocycle is absent. These results suggest that the ability of the molecule's side chain to adopt a beta-turn-like conformation may not be a prerequisite for biological activity in the didemnins and that conformations having an extended side-chain may play a role in the biological activity of aplidine.     

Chemical and radiochemical characterization of depleted uranium (DU) in Kosovo soils

As is well known ammunitions containing depleted uranium (DU) were used by NATO during the Balkan war. The paper deals with the determination of uranium alpha emitting radiosotopes in Kosovo soils by chemical separation and alpha spectrometry. The samples were collected by CISAM (Centro Interforze Studi ed Applicazioni Militari, S. Piero a Grado, Livorno) in the period November 1999-April 2000. The DU distribution in soil appeared very disomogeneous; the isotope weight percentages for U-238, U-235 and U-234 resulted 99.76, 0.24 and 7.24.10(-4) respectively; consequently the activity distribution was 86.42%, 1.31%, 11.63% and the isotope ratios were 1.52.10(-2) and 0.134 for U-235/U-238 and U-234/U-238 showing clearly the presence of DU. A small peak at 4.49 MeV (U-236) in the alpha spectrum indicated that the used DU was the by-product of exhausted uranium reprocessing. In order to determine the chemical and physiological solubility of uranium a fractionation study was carried out by using the Tessier method: 55% of uranium showed a fair solubility, but 45% was solubilized only by 8 M HNO3.     

Reductive lithiation of alkoxy-substituted benzyl methyl ethers and connection with cross-coupling reactions

2-and 4-Ethoxymethoxybenzyl methyl ethers were employied as useful starting materials for the synthesis of 1,2- or 1,4-dicarbo-substituted benzenes. The proposed reaction sequence involves connection between the reductive lithiation of benzyl alkyl ethers and the metal-catalyzed cross-coupling reaction of aromatic triflates.     

K18- and CAG-hACE2 Transgenic Mouse Models and SARS-CoV-2: Implications for Neurodegeneration Research

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that might lead to very serious consequences. Notably, mental status change, brain confusion, and smell and taste disorders along with neurological complaints have been reported in patients infected with SARS-CoV-2. Furthermore, human brain tissue autopsies from COVID-19 patients show the presence of SARS-CoV-2 neuroinvasion, which correlates with the manifestation of meningitis, encephalitis, leukocyte infiltration, and neuronal damage. The olfactory mucosa has been suggested as a way of entry into the brain. SARS-CoV-2 infection is also known to provoke a hyper-inflammatory reaction with an exponential increase in the production of pro-inflammatory cytokines leading to systemic responses, even in the absence of direct infection of brain cells. Angiotensin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, has been extensively demonstrated to be present in the periphery, neurons, and glial cells in different brain regions. To dissect the details of neurological complications and develop therapies helping COVID-19 survivors regain pre-infection quality of life, the development of robust clinical models is highly warranted. Several human angiotensin-converting enzyme 2 (hACE2) transgenic mouse models have been developed and used for antiviral drug screening and vaccine development, as well as for better understanding of the molecular pathogenetic mechanisms of SARS-CoV-2 infection. In this review, we summarize recent results from the studies involving two such mouse models, namely K18- and CAG-hACE2 transgenics, to evaluate the direct and indirect impact of SARS-CoV-2 infection on the central nervous system.     

Optimization of Direct Aromatic 18F-Labeling of Tetrazines

Radiolabeling of tetrazines has gained increasing attention due to their important role in pretargeted imaging or therapy. The most commonly used radionuclide in PET imaging is fluorine-18. For this reason, we have recently developed a method which enables the direct aromatic ¹⁸F-fluorination of tetrazines using stannane precursors through copper-mediated fluorinations. Herein, we further optimized this labeling procedure. 3-(3-fluorophenyl)-1,2,4,5-tetrazine was chosen for this purpose because of its high reactivity and respective limited stability during the labeling process. By optimizing parameters such as elution conditions, precursor amount, catalyst, time or temperature, the radiochemical yield (RCY) could be increased by approximately 30%. These conditions were then applied to optimize the RCY of a recently successfully developed and promising pretargeting imaging agent. This agent could be isolated in a decay corrected RCY of 14 ± 3% and Am of 201 ± 30 GBq/µmol in a synthesis time of 70 min. Consequently, the RCY increased by 27%.     

Effect of Bauhinia monandra Kurz Leaf Preparations on Embryonic Stages and Adult Snails of Biomphalaria glabrata (Say, 1818), Schistosoma mansoni Cercariae and Toxicity in Artemia salina

Biomphalaria glabrata snails constitute the main vector of schistosomiasis in Brazil, and Bauhinia monandra Kurz, the leaves of which contain BmoLL lectin with biocidal action, is a plant widely found on continents in which the disease is endemic. This work describes the composition of B. monandra preparations and the effect on embryos and adult snails, their reproduction parameters and hemocytes. We also describe the results of a comet assay after B. glabrata exposure to sublethal concentrations of the preparations. Additionally, the effects of the preparations on S. mansoni cercariae and environmental monitoring with Artemia salina are described. In the chemical evaluation, cinnamic, flavonoid and saponin derivatives were detected in the two preparations assessed, namely the saline extract and the fraction. Both preparations were toxic to embryos in the blastula, gastrula, trochophore, veliger and hippo stages (LC₅₀ of 0.042 and 0.0478; 0.0417 and 0.0419; 0.0897 and 0.1582; 0.3734 and 0.0974; 0.397 and 0.0970 mg/mL, respectively) and to adult snails (LC₅₀ of 6.6 and 0.87 mg/mL, respectively), which were reproductively affected with decreased egg deposition. In blood cell analysis, characteristic cells for apoptosis, micronucleus and binucleation were detected, while for comet analysis, different degrees of nuclear damage were detected. The fraction was able to cause total mortality of the cercariae and did not present environmental toxicity. Therefore, B. monandra preparations are promising in combating schistosomiasis since they can control both the intermediate host and eliminate the infectious agent, besides being safe to the environment.