Alkene–Azide 1,3‐Dipolar Cycloaddition as a Trigger for Ultrashort Peptide Hydrogel Dissolution

An alkene–azide 1,3‐dipolar cycloaddition between trans‐cyclooctene (TCO) and an azide‐capped hydrogel that promotes rapid gel dissolution is reported. Using an ultrashort aryl azide‐capped peptide hydrogel (PhePhe), we have demonstrated proof‐of‐concept where upon reaction with TCO, the hydrogel undergoes a gel–sol transition via 1,2,3‐triazoline degradation and 1,6‐self‐immolation of the generated aniline. The potential application of this as a general trigger in sustained drug delivery is demonstrated through release of encapsulated cargo (doxorubicin). Administration of TCO resulted in 87 % of the cargo being released in 10 h, compared to 13–14 % in the control gels. This is the first example of a potential bioorthogonal‐triggered hydrogel dissolution using a traditional click‐type reaction. This type of stimulus could be extended to other aryl azide‐capped hydrogels.     

DelPhi Suite: New Developments and Review of Functionalities

Electrostatic potential, energies, and forces affect virtually any process in molecular biology, however, computing these quantities is a difficult task due to irregularly shaped macromolecules and the presence of water. Here, we report a new edition of the popular software package DelPhi along with describing its functionalities. The new DelPhi is a C++ object-oriented package supporting various levels of multiprocessing and memory distribution. It is demonstrated that multiprocessing results in significant improvement of computational time. Furthermore, for computations requiring large grid size (large macromolecular assemblages), the approach of memory distribution is shown to reduce the requirement of RAM and thus permitting large-scale modeling to be done on Linux clusters with moderate architecture. The new release comes with new features, whose functionalities and applications are described as well. © 2019 The Authors. Journal of Computational Chemistry published by Wiley Periodicals, Inc.     

Expanding the scope of sulfur-centered Arbuzov rearrangement in diethyl/di-n-propyl sulfite for the synthesis of mixed-ligand di-n-butyltin alkanesulfonates

A one-pot reaction between di-n-butyltin oxide and diethyl/di-n-propyl sulfite in the presence of an equimolar amount of alkyl iodide proceeds via sulfur-centered Arbuzov rearrangement to afford the corresponding di-n-butyltin (alkoxy)alkanesulfonates n-Bu2Sn(OR')OS(O)2R [R = R' = Et (1), n-Pr (2); R = Me, R' = Et (3), n-Pr (4)]. The compounds 1 and 3 react with methylphosphonic acid under mild conditions to give [n-Bu2Sn(OS(O)2R)OP(O)(OH)Me]n [R = Et (5), Me (6), respectively].     

Superdeformed structures and low Ω parity doublet in Ne-S nuclei near neutron drip-line

The structures of Ne, Na, Mg, Al, Si, P and S nuclei near the neutron drip-line region are investigated in the frame-work of relativistic mean field theory and non-relativistic Skyrme Hartree-Fock formalism. The recently discovered nuclei ⁴⁰Mg and ⁴²Al, which are beyond the drip-line predicted by various mass formulae are located within these models. We find many largely deformed neutron-rich nuclei, whose structures are analyzed. From the structure anatomy, we find that at large deformation low orbits of opposite parities (e.g. $\frac{1} {2}^ +$ and $\frac{1} {2}^ -$ ) occur close to each other in energy.     

Polymeric stabilization of hybrid nanocomposites: a comparison between in situ and ex situ-grown CuInS2 in poly(3-hexylthiophene) polymer

CuInS₂ (CIS) particles were directly synthesized in P3HT matrix with different concentrations ratio of P3HT and CIS (1:2, 1:4, and 1:8) by decomposition of copper indium xanthate (CIX). Here, copper indium xanthate and P3HT were mixed homogeneously in o-dichlorobenzene (DCB), which induced the formation of the CIS nanoparticles by the thermal decomposition of the precursor compound in situ at temperatures as low as 110 °C. The effects of the precursor concentration on the size of the CIS nanoparticles was studied by microstructure investigations (TEM, AFM, XRD) and UV–vis measurements show that these CIS composites possess a direct bandgap energy higher than 1.45 eV depending on the concentration of P3HT. PL quenching of P3HT polymer (i.e., higher accessible fraction of fluorophores) was found to be more for in situ rather than ex situ conditions for comparable CIX concentrations or particle size. This can be attributed to the fact that in in situ synthesis, P3HT act as surface directing template for CIS nanoparticles which is not so in the case of ex situ synthesis. Due to this, the polymeric stabilization of the CIS nanocomposites is better realized for in situ synthesis as compared to ex situ synthesis.     

Efficient and Rapid Synthesis of Highly Functionalized Novel Symmetric 1,4-Dihydropyridines Using Glacial Acetic Acid as Solvent

A new series of 1,4-dihydropyridines bearing a pyrazole moiety in the 4-position were synthesized by a variation of the classical Hantzsch synthesis. The reaction of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde 4a–n with 3-amino crotononitrile in the presence of glacial acetic acid afforded novel 3,5-dicyano-2,6-dimethyl 1,4-dihydropyridines 5a–n. The procedure has short reaction time (15–20 min), easy workup, and good yield of product. The structures of all synthesized compounds were well characterized by mass, infrared, ¹H and ¹³C NMR, and elemental analysis.     

Carba-LNA-5MeC/A/G/T modified oligos show nucleobase-specific modulation of 3'-exonuclease activity, thermodynamic stability, RNA selectivity, and RNase H elicitation: synthesis and biochemistry

Using the intramolecular 5-exo-5-hexenyl radical as a key cyclization step, we previously reported an unambiguous synthesis of carba-LNA thymine (cLNA-T), which we subsequently incorporated in antisense oligonucleotides (AON) and investigated their biochemical properties [J. Am. Chem. Soc.2007, 129 (26), 8362-8379]. These cLNA-T incorporated oligos showed specific RNA affinity of +3.5-5 °C/modification for AON:RNA heteroduplexes, which is comparable to what is found for those of LNAs (Locked Nucleic Acids). These modified oligos however showed significantly enhanced nuclease stability (ca. 100 times more) in the blood serum compared to those of the LNA modified counterparts without compromising any RNase H recruitment capability. We herein report the synthesis of 5-methylcytosine-1-yl ((Me)C), 9-adeninyl (A), and 9-guaninyl (G) derivatives of cLNA and their oligonucleotides and report their biochemical properties as potential RNA-directed inhibitors. In a series of isosequential carba-LNA modified AONs, we herein show that all the cLNA modified AONs are found to be RNA-selective, but the magnitude of RNA-selectivity of 7'-R-Me-cLNA-G (cLNA-G) (ΔT(m) = 2.9 °C/modification) and intractable isomeric mixtures of 7'-(S/R)-Me-cLNA-T (cLNA-T, ΔT(m) = 2.2 °C/modification) was found to be better than diastereomeric mixtures of 7'-(S/R)-Me-cLNA-(Me)C with trace of cENA-(Me)C (cLNA-(Me)C, ΔT(m) = 1.8 °C/modification) and 7'-R-Me-cLNA-A (cLNA-A, ΔT(m) = 0.9 °C/modification). cLNA-(Me)C modified AONs however exhibited the best nuclease stability, which is 4-, 7-, and 20-fold better, respectively, than cLNA-T, cLNA-A, and cLNA-G modified counterparts, which in turn was more than 100 times stable than that of the native. When the modification sites are appropriately chosen in the AONs, the cLNA-A, -G, and -(Me)C modified sites in the AON:RNA hybrids can be easily recognized by RNase H, and the RNA strand of the hybrid is degraded in a specific manner, which is important for the design of oligos for therapeutic purposes. The cLNA-(Me)C modified AON/RNA, however, has been found to be degraded 4 times faster than cLNA-A and G modified counterparts. By appropriately choosing the carba-LNA modification sites in AON strands, the digestion of AON:RNA can be either totally repressed or be limited to cleavage at specific sites or at a single site only (similar to that of catalytic RNAzyme or DNAzyme). Considering all physico- and biochemical aspects of cLNA modified oligos, the work suggests that the cLNA modified antisense oligos have the potential of being a promising therapeutic candidate due to their (i) higher nucleobase-specific RNA affinity and RNA selectivity, (ii) greatly improved nuclease stability, and (iii) efficient RNase H recruitment capability, which can induce target RNA cleavage in a very specific manner at multiple or at a single site, in a designed manner.     

Hawking radiation,effective actions and covariant boundary conditions

From an appropriate expression for the effective action, the Hawking radiation from charged black holes is derived, using only covariant boundary conditions at the event horizon. The connection of our approach with the Unruh vacuum and the recent analysis [S.P. Robinson, F. Wilczek, Phys. Rev. Lett. 95 (2005) 011303, gr-qc/0502074; S. Iso, H. Umetsu, F. Wilczek, Phys. Rev. Lett. 96 (2006) 151302, hep-th/0602146; R. Banerjee, S. Kulkarni, arXiv: 0707.2449 [hep-th]] of Hawking radiation using anomalies is established.     

Combined effect of ultrasound and nanoclay on adsorption of phenol

Sorption of phenol onto organophilic bentonite (nanoclay) by ultrasonic irradiation was investigated. Tetrabutyl ammonium chloride (TBAC), N-acetyl-N,N,N trimethyl ammonium bromide (CTAB) and hexadecyl trimethyl ammonium chloride (HDTMA) were used as intercalating agents. Nanoclay was synthesized using sonication technique. TBAC modified nanoclay shows amorphous exfoliated nature, while CTAB and HDTMA modified nanoclay shows intercalating crystalline nature, which was revealed by XRD gram. Further FTIR reveals the presence of NH(2) and (CH(2))(n) groups onto clay platelet. Due to sonication, adsorption equilibrium was achieved within short period of time (10 min). It was found that intraparticle diffusion resistance has overcome due to sonication. The experimental data obtained obeys both Freundlich isotherm model and Langmuir adsorption isotherm model. HDTMA modified nanoclay shows higher parameter values.