Interaction between 14mer DNA oligonucleotide and cationic surfactants of various chain lengths

In the recent genomic era, a novel gene silencing approach has been introduced based on the use of small synthetic oligonucleotides, such as antisense RNAs, siRNAs, to inhibit the expression of a specific target gene. Successful implementation of this methodology calls for the development of efficient systems to deliver small oligonucleotides into the cells using various natural and synthetic cationic agents. While extensive studies have focused on the interaction of various natural and synthetic cationic surfactants with long DNA, less attention has been paid to surfactant interaction with small oligonucleotides. In this study, the interaction between 14mer double stranded DNA and alkyltrimethylammonium bromides of C16 (cetyl, CTAB), C14 (tetradecyl, TTAB), and C12 (dodecyl, DTAB) chain lengths was investigated at different charge ratios by gel electrophoresis, ethidium bromide exclusion, circular dichroism, and UV melting. Our gel studies at 1 microM oligonucleotide concentration showed that CTAB, TTAB, and DTAB neutralize the oligonucleotides at a charge ratio (Z+/-) of 1, 14, and 50, respectively. At lower charge ratios, CTAB and TTAB interact with oligonucleotides, and the complexes show electrophoretic mobility shifts in the gel, while such mobility shifts were completely absent in the case of DTAB. UV melting experiments revealed that interaction with all three surfactants increased the thermostability of the oligonucleotide. The extent of thermal stabilization was highest in the case of CTAB, moderate in the case of TTAB, and extremely low in the case of DTAB. Oligonucleotides within fully neutralized complexes denatured at further higher temperatures, and again, stabilization was the highest in the case of CTAB followed by TTAB and DTAB, hence revealing that the oligonucleotides interacted more strongly with CTAB than with the other two surfactants. Ethidium bromide exclusion studies also supported our UV melting studies, confirming that CTAB binds most strongly to the oligonucleotide. CD titrations of oligonucleotides with increasing amounts of surfactants revealed common spectral patterns consisting of the progressive loss of CD signals for native helical DNA conformations. Overall, our results demonstrate that interaction between oligonucleotides and cationic surfactants, although qualitatively similar to long double stranded DNA, shows subtle differences that need to be understood to improve small oligonucleotide delivery into the cells by using common delivery agents that have been used to deliver long pieces of DNA.     

Liquids with Permanent Macroporosity

Permanent macropores (>50 nm) had not been reported in the liquid state until a recent report by Tao Li and co-workers describing a synthetic strategy to form a porous liquid with dual micro-macroporosity. This is prepared by producing hierarchically porous particles that are surface coated and fluidised by dispersion. Surface micropores enable permanent porosity by steric exclusion of the fluid phase. The material has a considerable water uptake capacity (27 % w/w) due to large (480 nm) unoccupied macropores. This also enables switching of thermal conductivity on uptake of water. These are new properties translated from porous solids to the liquid state.     

Hybrid Improper Ferroelectricity in Columnar (NaY)MnMnTi4O12

We show that cation ordering on A site columns, oppositely displaced via coupling to B site octahedral tilts, results in a polar phase of the columnar perovskite (NaY)MnMnTi₄O₁₂. This scheme is similar to hybrid improper ferroelectricity found in layered perovskites, and can be considered a realisation of hybrid improper ferroelectricity in columnar perovskites. The cation ordering is controlled by annealing temperature and when present it also polarises the local dipoles associated with pseudo-Jahn–Teller active Mn²⁺ ions to establish an additional ferroelectric order out of an otherwise disordered dipolar glass. Below T_N≈12 K, Mn²⁺ spins order, making the columnar perovskites rare systems in which ordered electric and magnetic dipoles may reside on the same transition metal sublattice.     

Visible-Light-Triggered Photoswitching of Diphosphene Complexes

Although diphosphene transition metal complexes are known to undergo E to Z isomerization upon irradiation with UV light, their potential for photoswitching has remained poorly explored. In this study, we present diphosphene complexes capable of reversible photoisomerizations through haptotropic rearrangements. The compounds [( 2 -κ²P,κ⁶C)Mo(CO)₂][OTf] ( 3 a [OTf]), [( 2 -κ²P,κ⁶C)Fe(CO)][OTf] ( 3 b [OTf]), and [( 2 -κ²P)Fe(CO)₄][OTf] ( 4 [OTf]) were prepared using the triflate salt [(L_C)P=P(Dipp)][OTf] ( 2 [OTf) as a precursor (L_C=4,5-dichloro-1,3-bis(2,6-diisiopropylphenyl)-imidazolin-2-yl; Dipp=2,6-diisiopropylphenyl, OTf=triflate). Upon exposure to blue or UV light (λ=400 nm, 470 nm), the initially red-colored η²-diphosphene complexes 3 a , b [OTf] readily undergo isomerization to form blue-colored η¹-complexes [( 2 -κ¹P,κ⁶C)M(CO)_n][OTf] ( 5 a , b [OTf]; a : M=Mo, n=2; b : M=Fe, n=1). This haptotropic rearrangement is reversible, and the (κ²P,κ⁶C)-coordination mode gradually reverts back upon dissolution in coordinating solvents or more rapidly upon exposure to yellow or red irradiation (λ=590 nm, 630 nm). The electronic reasons for the reversible visible-light-induced photoswitching observed for 3 a , b [OTf] are elucidated by DFT calculations. These calculations indicate that the photochromic isomerization originates from the S₁ excited state and proceeds through a conical intersection.     

Crystal Structure and NMR of an α,δ-Peptide Foldamer Helix Shows Side-Chains are Well Placed for Bifunctional Catalysis: Application as a Minimalist Aldolase Mimic**

We report the first NMR and X-ray diffraction (XRD) structures of an unusual 13/11-helix (alternating i, i+1 {NH−O=C} and i, i+3 {C=O−H−N} H-bonds) formed by a heteromeric 1 : 1 sequence of α- and δ-amino acids, and demonstrate the application of this framework towards catalysis. Whilst intramolecular hydrogen bonds (IMHBs) are the clear driver of helix formation in this system, we also observe an apolar interaction between the ethyl residue of one δ-amino acid and the cyclohexyl group of the next δ-residue in the sequence that seems to stabilize one type of helix over another. To the best of our knowledge this type of additional stabilization leading to a specific helical preference has not been observed before. Critically, the helix type realized places the α-residue functionalities in positions proximal enough to engage in bifunctional catalysis as demonstrated in the application of our system as a minimalist aldolase mimic.     

Crystal Engineering of Two Light and Pressure Responsive Physisorbents

An emerging strategy in the design of efficient gas storage technologies is the development of stimuli-responsive physisorbents which undergo transformations in response to a particular stimulus, such as pressure, heat or light. Herein, we report two isostructural light modulated adsorbents (LMAs) containing bis-3-thienylcyclopentene (BTCP), LMA-1 [Cd(BTCP)(DPT)₂] (DPT=2,5-diphenylbenzene-1,4-dicarboxylate) and LMA-2 [Cd(BTCP)(FDPT)₂] (FDPT=5-fluoro-2,diphenylbenzene-1,4-dicarboxylate). Both LMAs undergo pressure induced switching transformations from non-porous to porous via adsorption of N₂, CO₂ and C₂H₂. LMA-1 exhibited multi-step adsorption while LMA-2 showed a single-step adsorption isotherm. The light responsive nature of the BTPC ligand in both frameworks was exploited with irradiation of LMA-1 resulting in a 55 % maximum reduction of CO₂ uptake at 298 K. This study reports the first example of a switching sorbent (closed to open) that can be further modulated by light.     

Assessment of hand-held Raman instrumentation for in situ screening for potentially counterfeit artesunate antimalarial tablets by FT-Raman spectroscopy and direct ionization mass spectrometry

Pharmaceutical counterfeiting has become a significant public health problem worldwide and new, rapid, user-friendly, reliable and inexpensive methods for drug quality screening are needed. This work illustrates the chemical characterization of genuine and fake artesunate antimalarial tablets by portable Raman spectroscopy and validation by FT-Raman spectroscopy and ambient mass spectrometry. The applicability of a compact and robust portable Raman spectrometer (TruScan™) for the in situ chemical identification of counterfeit tablets is reported.     

Disjoint Supercyclic Weighted Shifts

Complementing the existing literature in d-hypercyclicity, we characterize disjoint supercyclicity for a finite family of weighted shift operators. Using this characterization, we answer Question 2 in a recent paper by Bès, Martin and Peris in the negative by constructing examples of disjoint supercyclic weighted shifts whose direct sum operator is hypercyclic, but the same shifts operators fail to be disjoint hypercyclic. We also show the Disjoint Blow-Up/Collapse Property and the Strong Disjoint Blow-Up/Collapse Property for disjoint supercyclicity are equivalent when dealing with a finite family with two or more weighted shifts. However, those weighted shifts operators will never satisfy the Disjoint Supercyclicity Criterion. This provides a sharp distinction between disjoint supercyclicity and supercyclicity for a single operator. We provide a partial answer to disjoint supercyclic version of Question 3 in a recent paper by Salas by showing that we can always select an additional operator to add to an family of d-supercyclic weighted shift operators while maintaining the d-supercyclicity. We also show that, in general, this additional operator cannot be another weighted shift.     

A Chemical Probe for the ATAD2 Bromodomain

ATAD2 is a cancer‐associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF₂ as a sulfone bio‐isostere to exploit the unique properties of fluorine, and 2) using 1,3‐interactions to control the conformation of a piperidine ring. This resulted in the first reported low‐nanomolar, selective and cell permeable chemical probe for ATAD2.