Selective interactions of cationic porphyrins with G-quadruplex structures

G-quadruplex DNA presents a potential target for the design and development of novel anticancer drugs. Because G-quadruplex DNA exhibits structural polymorphism, different G-quadruplex typologies may be associated with different cellular processes. Therefore, to achieve therapeutic selectivity using G-quadruplexes as targets for drug design, it will be necessary to differentiate between different types of G-quadruplexes using G-quadruplex-interactive agents. In this study, we compare the interactions of three cationic porphyrins, TMPyP2, TMPyP3, and TMPyP4, with parallel and antiparallel types of G-quadruplexes using gel mobility shift experiments and a helicase assay. Gel mobility shift experiments indicate that TMPyP3 specifically promotes the formation of parallel G-quadruplex structures. A G-quadruplex helicase unwinding assay reveals that the three porphyrins vary dramatically in their abilities to prevent the unwinding of both the parallel tetrameric G-quadruplex and the antiparallel hairpin dimer G-quadruplex DNA by yeast Sgs1 helicase (Sgs1p). For the parallel G-quadruplex, TMPyP3 has the strongest inhibitory effect on Sgs1p, followed by TMPyP4, but the reverse is true for the antiparallel G-quadruplex. TMPyP2 does not appear to have any effect on the helicase-catalyzed unwinding of either type of G-quadruplex. Photocleavage experiments were carried out to investigate the binding modes of all three porphyrins with parallel G-quadruplexes. The results reveal that TMPyP3 and TMPyP4 appear to bind to parallel G-quadruplex structures through external stacking at the ends rather than through intercalation between the G-tetrads. Since intercalation between G-tetrads has been previously proposed as an alternative binding mode for TMPyP4 to G-quadruplexes, this mode of binding, versus that determined by a photocleavage assay described here (external stacking), was subjected to molecular dynamics calculations to identify the relative stabilities of the complexes and the factors that contribute to these differences. The DeltaG(o) for the external binding mode was found to be driven by DeltaH(o) with a small unfavorable TDeltaS(o) term. The DeltaG(o) for the intercalation binding model was driven by a large TDeltaS(o) term and complemented by a small DeltaH(o) term. One of the main stabilizing components of the external binding model is the energy of solvation, which favors the external model over the intercalation model by -67.94 kcal/mol. Finally, we propose that intercalative binding, although less favored than external binding, may occur, but because of the nature of the intercalative binding, it is invisible to the photocleavage assay. This study provides the first experimental insight into how selectivity might be achieved for different G-quadruplexes by using structural variants within a single group of G-quadruplex-interactive drugs.     

Application of Polyphosphoric Acid‐Mediated Acyl Migration for Regiospecific Synthesis of Diverse 2‐Acylpyrroles from Chalcones

A metal‐free approach for the synthesis of 2‐acylpyrroles is reported in this paper. Synthesis of the target molecule started from chalcones and was carried out in two steps. Initial step involved the conversion of chalcones to corresponding 4‐substituted‐3‐acylpyrroles by reaction with TosMIC. In the subsequent step, target molecules were obtained in modest to good yields by polyphosphoric acid‐mediated acyl rearrangement of 3‐acylpyrroles to their 2‐acyl congeners. The crucial final step was amenable to diverse substitutions on pyrrole ring. Preliminary experiment for the determination of mechanism indicated the involvement of acylium ion.     

Symphony of kinetics and statistical design approaches for response analysis during tray drying of Lagenaria siceraria leaves

Journal of Thermal Analysis and Calorimetry - Drying characteristics of horticultural produce often target studies on the process parameters so as to derive useful data for the development of...     

Charged particle multiplicity distributions ine + e − annihilation at 29 GeV: a comparison with hadronic data

The charged particle multiplicity distributions for two-jet events ine ⁺ e ^? annihilation at 29 GeV have been measured using the High Resolution Spectrometer at PEP. A Poisson distribution describes the data for both the complete event and for the single jets. In addition, no correlation is observed between the multiplicities in the two jets of an event. For fixed values of the prong number of the complete event, the multiplicity sharing between the two jets is in good agreement with a binomial distribution. The rapidity gap distribution is exponential with a slope equal to the mean rapidity density. These observations, which are consistent with a picture of independent emission of single particles, are contrasted to the results from soft hadronic collisions and conclusions are drawn about the nature of clusters.     

Surface and Structural Investigation of a MnOx Birnessite‐Type Water Oxidation Catalyst Formed under Photocatalytic Conditions

Catalytically active MnO_x species have been reported to form in situ from various Mn‐complexes during electrocatalytic and solution‐based water oxidation when employing cerium(IV) ammonium ammonium nitrate (CAN) oxidant as a sacrificial reagent. The full structural characterization of these oxides may be complicated by the presence of support material and lack of a pure bulk phase. For the first time, we show that highly active MnO_x catalysts form without supports in situ under photocatalytic conditions. Our most active ⁴MnO_x catalyst (～0.84 mmol O₂ mol Mn^?1 s^?1) forms from a Mn₄O₄ bearing a metal–organic framework. ⁴MnO_x is characterized by pair distribution function analysis (PDF), Raman spectroscopy, and HR‐TEM as a disordered, layered Mn‐oxide with high surface area (216 m²g^?1) and small regions of crystallinity and layer flexibility. In contrast, the ^SMnO_x formed from Mn²⁺ salt gives an amorphous species of lower surface area (80 m²g^?1) and lower activity (～0.15 mmol O₂ mol Mn^?1 s^?1). We compare these catalysts to crystalline hexagonal birnessite, which activates under the same conditions. Full deconvolution of the XPS Mn2p_3/2 core levels detects enriched Mn³⁺ and Mn²⁺ content on the surfaces, which indicates possible disproportionation/comproportionation surface equilibria.     

S-wave structure in the Kπ system

We have analysed the Kπ spectrum (4 827 events) of the reaction K⁺n→K⁺π^?p at 9 GeV/c and find evidence of a broad S-wave enhancement which may be interpreted as a resonance. For production of Kπ masses above 890 GeV/c², we have assumed the dominance of pion exchange.     

The reaction Kp→Λπ in the c.m. energy range 1915 to 2168 MeV

A formationstudy of the reaction K⁻p→Λπ^o at 13 c.m. energies between 1915 and 2168 MeV is presented. Experimental differential cross sections and polarizations are given as expansions of Legendre polynomials and associated Legendre polynomials respectively. Partial wave analysis confirms the assignment of the Σ(2030) and the assignment of the Σ(1915). The parameters of these resonances are determined. The possible existence of other resonances coupled to this channel is investigated.