The Quenched Asymptotics for Nonlocal Schrödinger Operators with Poissonian Potentials

Potential Analysis - We study the quenched long time behaviour of the survival probability up to time t, $\mathbf {E}_{x}\left [e^{-{{\int }_{0}^{t}} V^{\omega }(X_{s})\mathrm {d}s}\right ],$ of a...     

Minimizing Side Product Formation in Alkyne Functionalization of Ruthenium Complexes by Introduction of Protecting Groups

The synthesis of alkyne functionalized bipyridine ruthenium complexes are reported. The improved synthetic approach through application of stable protecting groups prevents formation of possible side products while facilitating purification. By applying copper-catalysed azide-alkyne cycloaddition reactions (CuAAC) pyrene units with flexible alkyl linkers are introduced at the periphery of the complex, opening up various applications including surface immobilization and DNA intercalation. All complexes are characterized structurally as well as photophysically, especially regarding the influence of the introduced alkyne and triazolyl substituents on their photophysical behavior.     

Acetate platinum(II) compound with 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine that overcomes cisplatin resistance: structural characterization,in vitro cytotoxicity,and kinetic studies

The reaction of silver acetate with cis-[PtI₂(dbtp)₂], where dbtp = 5,7-ditertbutyl-1,2,4-triazolo-[1,5-a]pyrimidine, yielded cis-[Pt(OOCCH₃)₂(dbtp)₂]·dmf (1). The complex has been analyzed by multinuclear magnetic resonance (¹H, ¹³C, ¹⁵N), IR, and Raman. The compound formed two rotamers in CDCl₃ and its spatial structures have been optimized using computational calculation. It was found that head-to-tail rotamer (1a) is more stable than its head-to-head counterpart (1b). In vitro antiproliferative activity against four tumor cell lines (A549, T47D, FaDu, and A2780cis) revealed in all cases significant cytotoxicity (IC₅₀ = 0.26–1.80 μM), possessing IC₅₀ values at least fivefold lower than cisplatin, carboplatin, and oxaliplatin (except A2780cis). The remarkable in vitro activity against T47D and A2780cis suggested the ability to overcome cisplatin resistance in these types of tumor cells. In addition, in vitro toxicity was evaluated against BALB/3T3 and has shown that the lipophilic platinum(II) complex (1) inhibits cell proliferation weaker than cisplatin and oxaliplatin. Additionally, cis-[Pt(OOCCH₃)₂(dbtp)₂]·dmf exhibited selective activity, in contrast to cisplatin or oxaliplatin.     

Are there reliable DFT approaches for 13C NMR chemical shift predictions of fullerene C60 derivatives?

The relationships between experimental and theoretical ¹³C NMR chemical shifts of a pristine fullerene C₆₀, monoadducts from [2 + n] cycloaddition (n = 1–3), and one [2 + 1] bis‐adduct are systematically analyzed for the first time by using diverse quantum‐chemical levels of theory. These levels involved B3LYP, B3PW91, B97‐2, mPW1PW91, PBE1PBE, and X3LYP hybrid functionals combined with 3‐21G, 6‐31G, 6‐31G(d), 6‐31G(d,p), 6‐31G(d,2p), LanL2DZ, and SDDAll basis sets. X3LYP/6‐31G approach is determined to have the lowest deviations from the ¹³C NMR experimental data compared to the other methods for all the fullerene compounds (mean absolute error value is 0.856 ppm and root mean squared error value is 1.197 ppm). The highest deviations are characteristic for α (sp² C2/C5/C8/C10) and β (sp² C6/C7/C11/C12) carbon atoms relative to a functionalization site and for those (sp³ C1/C9) directly attached with a side fragment in the [2 + n] monoadducts (n = 1–3). A probable reason of such deviation is that the approaches do not take into account a contribution of paramagnetic ring currents to ¹³C NMR chemical shifts. The results will be useful in design of novel fullerene derivatives and in performing unambiguous ¹³C NMR chemical shift assignments with modern quantum chemistry calculations.     

Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.     

Optimization of Pressurized Liquid Extraction of Lycopodiaceae Alkaloids Obtained from Two Lycopodium Species

Alkaloids of the Lycopodiaceae family are of great interest to researchers due to their numerous properties and wide applications in medicine. They play a very important role mainly due to their potent antioxidant, antidepressant effects and a reversible ability to inhibit acetylcholinesterase (AChE) enzyme activity. This property is of immense importance due to the growing problem of an increasing number of patients with neurodegenerative diseases in developed countries and a lack of effective and efficient treatment for them. Numerous studies have shown that Lycopodiaceae alkaloids are a rich source of AChE inhibitors. In the obtaining of new therapeutic phytochemicals from plant material, the extraction process and its efficiency is crucial. Therefore, the aim of this work was to optimize the conditions of modern PLE to obtain bioactive alkaloids from two Lycopodium species: L. clavatum L. and L. annotinum L. Five different solvents of different polarity were used for prepared plant extracts in order to compare the alkaloid content in and thereby effectiveness of the entire extraction. PLE parameters were used based on multiple studies conducted that gave the highest alkaloids recovery. Crude extracts were purified using solid-phase extraction (SPE) on Oasis HLB cartridge and examined by HPLC/ESI-QTOF–MS of the highly abundant alkaloids. To the best of our knowledge, this is the first time such high recoveries have been obtained for known Lycopodiaceae alkaloids. The best extraction results of alkaloid-lycopodine were detected in the dichloromethane extract from L. clavatum, where the yield exceeded 45%. The high recovery of annotinine above 40% presented in L. annotinum was noticed in dichloromethane and ethyl acetate extracts. Moreover, chromatograms were obtained with all isolated alkaloids and the best separation and quality of the bands in methanolic extracts. Interestingly, no alkaloid amounts were detected in cyclohexane extracts belonging to the non-polar solvent. These results could be helpful for understanding and optimizing the best conditions for isolating potent AChE inhibitors.     

Discovery of Potential,Dual-Active Histamine H3 Receptor Ligands with Combined Antioxidant Properties

In an attempt to find new dual acting histamine H₃ receptor (H₃R) ligands, we designed a series of compounds, structurally based on previously described in our group, a highly active and selective human histamine H₃ receptor (hH₃R) ligand KSK63. As a result, 15 obtained compounds show moderate hH₃R affinity, the best being the compound 17 (hH₃R K_i = 518 nM). Docking to the histamine H₃R homology model revealed two possible binding modes, with key interactions retained in both cases. In an attempt to find possible dual acting ligands, selected compounds were tested for antioxidant properties. Compound 16 (hH₃R K_i = 592 nM) showed the strongest antioxidant properties at the concentration of 10⁻⁴ mol/L. It significantly reduced the amount of free radicals presenting 50–60% of ascorbic acid activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, as well as showed antioxidative properties in the ferric reducing antioxidant power (FRAP) assay. Despite the yet unknown antioxidation mechanism and moderate hH₃R affinity, 16 (QD13) constitutes a starting point for the search of potential dual acting H₃R ligands-promising tools for the treatment of neurological disorders associated with increased neuronal oxidative stress.     

Unlocking the Hydrolytic Mechanism of GH92 α-1,2-Mannosidases: Computation Inspires the use of C-Glycosides as Michaelis Complex Mimics

The conformational changes in a sugar moiety along the hydrolytic pathway are key to understand the mechanism of glycoside hydrolases (GHs) and to design new inhibitors. The two predominant itineraries for mannosidases go via ^OS₂→B_2,5→¹S₅ and ³S₁→³H₄→¹C₄. For the CAZy family 92, the conformational itinerary was unknown. Published complexes of Bacteroides thetaiotaomicron GH92 catalyst with a S-glycoside and mannoimidazole indicate a ⁴C₁→⁴H₅/¹S₅→¹S₅ mechanism. However, as observed with the GH125 family, S-glycosides may not act always as good mimics of GH's natural substrate. Here we present a cooperative study between computations and experiments where our results predict the E₅→B_2,5/¹S₅→¹S₅ pathway for GH92 enzymes. Furthermore, we demonstrate the Michaelis complex mimicry of a new kind of C-disaccharides, whose biochemical applicability was still a chimera.