Cytotoxicity of Amino-BODIPY Modulated via Conjugation with 2-Phenyl-3-Hydroxy-4(1H)-Quinolinones

The combination of cytotoxic amino-BODIPY dye and 2-phenyl-3-hydroxy-4(1H)-quinolinone (3-HQ) derivatives into one molecule gave rise to selective activity against lymphoblastic or myeloid leukemia and the simultaneous disappearance of the cytotoxicity against normal cells. Both species′ conjugation can be realized via a disulfide linker cleavable in the presence of glutathione characteristic for cancer cells. The cleavage liberating the free amino-BODIPY dye and 3-HQ derivative can be monitored by ratiometric fluorescence or by the OFF-ON effect of the amino-BODIPY dye. A similar cytotoxic activity is observed when the amino-BODIPY dye and 3-HQ derivative are connected through a non-cleavable maleimide linker. The work reports the synthesis of several conjugates, the study of their cleavage inside cells, and cytotoxic screening.     

UiO-66 and hcp UiO-66 Catalysts Synthesized from Ionic Liquids as Linker Precursors

Using ionic liquids (ILs) as linker precursors, the well-known metal-organic framework (MOF) UiO-66 (Universitetet i Oslo) and the recently reported MOF hcp UiO-66 (hexagonal closed packed) have been successfully synthesized and characterized. The advantage of the applied novel synthesis approach is an economically and environmentally benign work-up procedure, due to the better solubility of the IL. Additionally, the reactivity of the terephthalate anions is increased compared to terephthalic acid, resulting in faster MOF formation with an increased amount of defects in the MOF structure. In order to explore to the influence of defects on the catalytic performance, the cyclisation of citronellal to isopulegol was employed as test reaction. The activity of hcp UiO-66 and fcc UiO-66 (face centered cubic) is improved compared to other MOF or zeolite based catalysts, while the selectivity is similar.     

Layer-by-layer sensor architecture of polymers and nanoparticles for electrochemical detection of uric acid in human urine samples

Excessive uric acid levels in the human body (hyperuricemia) are the main causes of kidney stones and diabetes. In this study, a layer-by-layer arrangement of polymers and nanocomposites is used as a new electrode sensing material for rapid and direct electrochemical determination of uric acid (UA). The electrode surface architecture was constructed by the incorporation of poly (amidoamine) dendrimer with 0.5 generation (poly (amidoamine) [PAMAM] [D-G0.5]) of multiwalled carbon nanotube-silver nanoparticles (MWCNT-AgNP) and a poly (neutral-red) (poly [NR]) polymer. The PAMAM (D-G0.5)/MWCNT-AgNP/poly (NR)-coated electrode has a good electrocatalytic activity for the determination of UA using cyclic voltammetry and showed remarkable enhancement in current response at a low-oxidation potential (0.3 V). Under optimal conditions, the developed electrochemical sensor showed an excellent and wide linear range for the determination of UA (i.e. 0.016 μM–2500 μM), and the limit of detection was found to be 0.005 μM. The modified sensor system demonstrated excellent sensitivity and selectivity toward the detection of UA in the presence of interfering substances, which are commonly found in urine and human fluid samples. Furthermore, the developed sensor has represented both reproducibility and excellent stability for the UA determination in real samples (human urine).     

Chemical Conversion of Hardly Ionizable Rhenium Aryl Chlorocomplexes with p-Substituted Anilines

Fast and selective analytical methods help to ensure the chemical identity and desired purity of the prepared complexes before their medical application, and play an indispensable role in clinical practice. Mass spectrometry, despite some limitations, is an integral part of these methods. In the context of mass spectrometry, specific problems arise with the low ionization efficiency of particular analytes. Chemical derivatization was used as one of the most effective methods to improve the analyte’s response and separation characteristics. The Schotten–Baumann reaction was successfully adapted for the derivatization of ESI hardly ionizable Re(VII) bis(catechol) oxochlorocomplex. Various alkyl and halogen p-substituted anilines as possible derivatization agents were tested. Unlike the starting complex, the reaction products were easily ionizable in electrospray, providing structurally characteristic molecular and fragment anions. DFT computer modeling, which proposed significant conformation changes of prepared complexes within their deprotonation, proved to have a close link to MS spectra. High-resolution MS and MS/MS measurements complemented with collision-induced dissociation experiments for detailed specification of prepared complexes’ fragmentation pathways were used. The specified fragmentation schemes were analogous for all studied derivatives, with an exception for [Re(O)(Cat)₂PIPA].     

Investigating the Disordered and Membrane-Active Peptide A-Cage-C Using Conformational Ensembles

The driving forces and conformational pathways leading to amphitropic protein-membrane binding and in some cases also to protein misfolding and aggregation is the subject of intensive research. In this study, a chimeric polypeptide, A-Cage-C, derived from α-Lactalbumin is investigated with the aim of elucidating conformational changes promoting interaction with bilayers. From previous studies, it is known that A-Cage-C causes membrane leakages associated with the sporadic formation of amorphous aggregates on solid-supported bilayers. Here we express and purify double-labelled A-Cage-C and prepare partially deuterated bicelles as a membrane mimicking system. We investigate A-Cage-C in the presence and absence of these bicelles at non-binding (pH 7.0) and binding (pH 4.5) conditions. Using in silico analyses, NMR, conformational clustering, and Molecular Dynamics, we provide tentative insights into the conformations of bound and unbound A-Cage-C. The conformation of each state is dynamic and samples a large amount of overlapping conformational space. We identify one of the clusters as likely representing the binding conformation and conclude tentatively that the unfolding around the central W23 segment and its reorientation may be necessary for full intercalation at binding conditions (pH 4.5). We also see evidence for an overall elongation of A-Cage-C in the presence of model bilayers.     

Prebiotic Route to Thymine from Formamide—A Combined Experimental–Theoretical Study

Synthesis of RNA nucleobases from formamide is one of the recurring topics of prebiotic chemistry research. Earlier reports suggest that thymine, the substitute for uracil in DNA, may also be synthesized from formamide in the presence of catalysts enabling conversion of formamide to formaldehyde. In the current paper, we show that to a lesser extent conversion of uracil to thymine may occur even in the absence of catalysts. This is enabled by the presence of formic acid in the reaction mixture that forms as the hydrolysis product of formamide. Under the reaction conditions of our study, the disproportionation of formic acid may produce formaldehyde that hydroxymethylates uracil in the first step of the conversion process. The experiments are supplemented by quantum chemical modeling of the reaction pathway, supporting the plausibility of the mechanism suggested by Saladino and coworkers.     

Effects of accelerated carbonation on properties of ceramic-based geopolymers

Journal of Thermal Analysis and Calorimetry - Geopolymers are considered as environmentally friendly binders with a high potential not only to lower the prices of binders, but mainly to decrease...     

Selected Thoughts on Hydrophobicity in Drug Design

The fundamental aim of drug design in research and development is to invent molecules with selective affinity towards desired disease-associated targets. At the atomic loci of binding surfaces, systematic structural variations can define affinities between drug candidates and biomolecules, and thereby guide the optimization of safety, efficacy and pharmacologic properties. Hydrophobic interaction between biomolecules and drugs is integral to binding affinity and specificity. Examples of antiviral drug discovery are discussed.     

Hydrazones of 4-(Trifluoromethyl)benzohydrazide as New Inhibitors of Acetyl- and Butyrylcholinesterase

Based on the broad spectrum of biological activity of hydrazide–hydrazones, trifluoromethyl compounds, and clinical usage of cholinesterase inhibitors, we investigated hydrazones obtained from 4-(trifluoromethyl)benzohydrazide and various benzaldehydes or aliphatic ketones as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). They were evaluated using Ellman’s spectrophotometric method. The hydrazide–hydrazones produced a dual inhibition of both cholinesterase enzymes with IC₅₀ values of 46.8–137.7 µM and 19.1–881.1 µM for AChE and BuChE, respectively. The majority of the compounds were stronger inhibitors of AChE; four of them (2-bromobenzaldehyde, 3-(trifluoromethyl)benzaldehyde, cyclohexanone, and camphor-based 2o, 2p, 3c, and 3d, respectively) produced a balanced inhibition of the enzymes and only 2-chloro/trifluoromethyl benzylidene derivatives 2d and 2q were found to be more potent inhibitors of BuChE. 4-(Trifluoromethyl)-N’-[4-(trifluoromethyl)benzylidene]benzohydrazide 2l produced the strongest inhibition of AChE via mixed-type inhibition determined experimentally. Structure–activity relationships were identified. The compounds fit physicochemical space for targeting central nervous systems with no apparent cytotoxicity for eukaryotic cell line together. The study provides new insights into this CF₃-hydrazide–hydrazone scaffold.