Loss of Hoogsteen pairing ability upon N1 adenine platinum binding

Chloroform- and Freon-soluble mixed thymine, adenine complexes trans-[Pt(MeNH(2))(2)(ChmT-N3)(ChmA-N1)]NO(3) (2) and trans-[Pt(MeNH(2))(2)(ChmT-N3)(TBDMS-ado-N1)]BF(4) (3) (ChmT = anion of 1-cyclohexylmethylthymine ChmTH, ChmA = 9-cyclohexylmethyladenine, TBDMS-ado = 2',3',5'-tri-tert-butyldimethylsilyladenosine) have been prepared and characterized to study their propensity to undergo Hoogsteen and/or reversed Hoogsteen pairing in solution with free ChmTH and free 3',5'-diacetyl-2'-deoxyuridine, respectively. No Hoogsteen or reversed Hoogsteen pairing between 2 and ChmT takes place in CDCl(3). In Freon, partial H bonding between N1 platinated TBDMS-ado and 3',5'-diacetyl-2'-deoxyuridine as well as its [3-(15)N] labeled analogue is unambiguously observed only below 150 K. Comparison of (1)J ((15)N-(1)H) coupling constants of 3',5'-diacetyl-2'-deoxyuridine involved in Hoogsteen pairing with free and N1 platinated adenine suggests that the interaction is inherently weaker in the case of platinated adenine. To better understand the complete absence of hydrogen bonding between the ChmA ligand in 2 and free ChmTH, ab initio calculations (gas phase, 0 K) have been carried out for Hoogsteen pairs involving adenine (A) and thymine (T), as well as simplified analogues of 2 and T, both in the presence and absence of counteranions. The data strongly suggest that reduction of the effective positive charge of the heavy metal ion Pt(2+) by counterions diminishes interaction energies. With regard to mixtures of 2 and ChmTH in chloroform, this implies that ion pair formation between the cation of 2 and NO(3)(-) may be responsible for the lack of any measurable Hoogsteen pairing in this solvent.     

Tetraloop‐like Geometries Could Form the Basis of the Catalytic Activity of the Most Ancient Ribooligonucleotides

The origin of the catalytic activity of ancient oligonucleotides is a largely unexplored field of contemporary science. In the current work we use molecular dynamics simulations to investigate the plausibility of tetraloop‐like overhang geometries to initiate transphosphorylation reactions that lead to ligation and terminal cleavage in simple, Watson–Crick (WC) complementary oligoC/oligoG sequences observed experimentally. We show a series of examples of known tetraloop architectures, which can be adopted by the unpaired overhangs of short oligonucleotide sequences for a sufficiently long time to enable chemical reactions that lead to simple ribozyme‐like catalytic activity. Thus, our computations demonstrate that the role of non‐WC interactions at the emergence of the most ancient catalytic oligonucleotides could be more significant than ever believed.     

Fluorescence of a Histidine-Modified Enhanced Green Fluorescent Protein (EGFP) Effectively Quenched by Copper(II) Ions

Two histidines were introduced by site-directed mutagenesis into the structure of Enhanced Green Fluorescent Protein, replacing the serine at position 202 and the glutamine at position 204 for increasing the sensitivity of the protein towards different metal ions by creating possible metal binding sites near the chromophore group. There is no appreciable difference between the absorbance and fluorescence spectra of the two proteins (wild type and the double-histidine mutant) indicating that the mutation does not change the environment of the fluorophore. Fluorescence quenching was measured at different pH (6.5–8) and temperatures (20–45 °C) varying the concentration of metal ions. Under optimal conditions (pH?=?7.5, 20 °C) the mutant’s K_d is 16 nM, it binds copper more than 200fold stronger than the wild type EGFP.     

Novel Method for the High-Yielding Synthesis of Steroidal Hydroxamic acid Derivatives

Steroidal 17-hydroxamic acid derivatives were synthesized in high yields in palladium-catalysed carbonylation reaction of 17-iodo-androst-16-ene derivatives under mild reaction conditions.     

A concise synthesis of indoloquinoline skeletons applying two consecutive Pd-catalyzed reactions

The indoloquinoline alkaloids cryptolepine (1), neocryptolepine (2), isocryptolepine (3), and isoneocryptolepine (4) are important tools in traditional medicine. Now, their precursors 1a–4a were synthesized in two steps starting from the corresponding bromo-iodoquinolines. Our strategy is based on palladium-catalyzed reactions, applying regioselective Buchwald–Hartwig amination on 2,3- and 3,4-dihaloquinolines followed by an intramolecular Heck-type reaction. Both steps were carried out under microwave irradiation.     

Microwave-Assisted Synthesis of Organophosphorus Compounds

Abstract

Kabachnik-Fields reactions of a variety of amines, phospha-Michael additions to maleimide derivatives and alcoholysis of dialkyl phosphites were studied under microwave conditions.     

Modeling the effect of molecular architecture of comb polymers on the behavior of Al2O3 dispersions using charge/composition factors (CCF)

In this work, we study the effect of periodicity and PEO side-chain length in four PMAA-PEO (sodium salt) comb polymers with known molecular architecture on Al₂O₃ colloidal dispersions in DI water. We introduce here charge composition factors (CCF) representing charge density of the comb polymers defined as (number of charged units in a repeating unit)/(molecular weight of a repeating unit). We find, for the first time to our knowledge, that the CCF can be used along with dispersant dosage to obtain explicit functions predicting the conductivity of the dispersants in solution, the zeta potential behavior during dispersant titrations, and the isoelectric point (IEP) of the dispersions. In addition, the dosage normalized by the CCF provides a basis for comparison for the dispersants to elucidate the trends found in adsorption and potentiometric titrations. Thus, the CCF can be used as a tool for the design of improved and new comb polymer molecular architectures.     

In Vitro Tests of FDM 3D-Printed Diclofenac Sodium-Containing Implants

One of the most promising emerging innovations in personalized medication is based on 3D printing technology. For use as authorized medications, 3D-printed products require different in vitro tests, including dissolution and biocompatibility investigations. Our objective was to manufacture implantable drug delivery systems using fused deposition modeling, and in vitro tests were performed for the assessment of these products. Polylactic acid, antibacterial polylactic acid, polyethylene terephthalate glycol, and poly(methyl methacrylate) filaments were selected, and samples with 16, 19, or 22 mm diameters and 0%, 5%, 10%, or 15% infill percentages were produced. The dissolution test was performed by a USP dissolution apparatus 1. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide dye (MTT)-based prolonged cytotoxicity test was performed on Caco-2 cells to certify the cytocompatibility properties. The implantable drug delivery systems were characterized by thermogravimetric and heatflow assay, contact angle measurement, scanning electron microscopy, microcomputed tomography, and Raman spectroscopy. Based on our results, it can be stated that the samples are considered nontoxic. The dissolution profiles are influenced by the material properties of the polymers, the diameter, and the infill percentage. Our results confirm the potential of fused deposition modeling (FDM) 3D printing for the manufacturing of different implantable drug delivery systems in personalized medicine and may be applied during surgical interventions.     

Synthesis of New Quinoline Derivatives

The synthesis of some new functionalized quinolyl derivatives has been described, based on the 1,3‐dipolar cycloaddition of an azomethine ylide, generated from sarcosine or N‐benzylglycine and paraformaldehyde, to 2‐chloro‐3‐quinolinecarbaldehydes.