Engineering Porosity and Functionality in a Robust Twofold Interpenetrated Bismuth-Based MOF: Toward a Porous, Stable, and Photoactive Material.

Defect engineering in metal-organic frameworks (MOFs) has gained worldwide research traction, as it offers tools to tune the properties of MOFs. Herein, we report a novel 2-fold interpenetrated Bi-based MOF made of a tritopic flexible organic linker, followed by missing-linker defect engineering. This procedure creates a gradually augmented micro- and mesoporosity in the parent (originally nonporous) network. The resulting MOFs can tolerate a remarkable extent of linker vacancy (with absence of up to 60% of linkers per Bi node) created by altering the crystal-growth rate as a function of synthesis temperature and duration. Owing to the enhanced porosity and availability of the uncoordinated Lewis acidic Bi sites, the defect-engineered MOFs manifested improved surface areas, augmented CO2 and water vapor uptake, and catalytic activity. Parallel to this, the impact of defect engineering on the optoelectronic properties of these MOFs has also been studied, offering avenues for new applications.

Decoding Excimer Formation in Covalent-Organic Frameworks Induced by Morphology and Ring Torsion.

A thorough and quantitative understanding of the fate of excitons in covalent-organic frameworks (COFs) after photoexcitation is essential for their augmented optoelectronic and photocatalytic applications via precise structure tuning. The synthesis of a library of COFs having identical chemical backbone with impeded conjugation, but varied morphology and surface topography to study the effect of these physical properties on the photophysics of the materials is herein reported. The variation of crystallite size and surface topography substantified different aggregation pattern in the COFs, which leads to disparities in their photoexcitation and relaxation properties. Depending on aggregation, an inverse correlation between bulk luminescence decay time and exciton binding energy of the materials is perceived. Further transient absorption spectroscopic analysis confirms the presence of highly localized, immobile, Frenkel excitons (of diameter 0.3-0.5 nm) via an absence of annihilation at high density, most likely induced by structural torsion of the COF skeletons, which in turn preferentially relaxes via long-lived (nanosecond to microsecond) excimer formation (in femtosecond scale) over direct emission. These insights underpin the importance of structural and topological design of COFs for their targeted use in photocatalysis.

Structural Requirements for Reverse Transcription by a Diversity-generating Retroelement.

Diversity-generating retroelements (DGRs), which are pervasive among microbes, create massive protein sequence variation through reverse transcription of a protein-coding RNA template coupled to frequent misincorporation at template adenines. For cDNA synthesis, the template must be surrounded by up- and downstream sequences. Cryo-EM revealed that this longer RNA formed an integral ribonucleoprotein (RNP) with the DGR reverse transcriptase bRT and associated protein Avd. The downstream, noncoding (nc) RNA formed stem-loops enveloping bRT and laying over barrel-shaped Avd, and duplexes with the upstream and template RNA. These RNA structural elements were required for reverse transcription, and several were conserved in DGRs from distant taxa. Multiple RNP conformations were visualized, and no large structural rearrangements occurred when adenine replaced guanine as the template base, suggesting energetics govern misincorporation at adenines. Our results explain how the downstream ncRNA primes cDNA synthesis, promotes processivity, terminates polymerization, and stringently limits mutagenesis to DGR variable proteins.

Super-Oxidizing Covalent Triazine Framework Electrocatalyst for Two-Electron Water Oxidation to H2 O2.

Electrochemical two-electron water oxidation (2e WOR) is gaining surging research traction for sustainable hydrogen peroxide production. However, the strong oxidizing environment and thermodynamically competitive side-reaction (4e WOR) posit as thresholds for the 2e WOR. We herein report a custom-crafted covalent triazine network possessing strong oxidizing properties as a proof-of-concept metal-free functional organic network electrocatalyst for catalyzing 2e WOR. As the first-of-its-kind, the material shows a maximum of 89.9 % Faradaic Efficiency and 1428 µmol/h/cm2 H2 O2 production rate at 3.0 V bias potential (vs reversible hydrogen electrode, RHE), which are either better or comparable to the state-of-the-art electrocatalysts. We have experimentally confirmed a stepwise 2e WOR mechanism which was further computationally endorsed by density functional theory studies.

Pyrene-Based Covalent Organic Frameworks for Photocatalytic Hydrogen Peroxide Production.

Four highly porous covalent organic frameworks (COFs) containing pyrene units were prepared and explored for photocatalytic H2 O2 production. The experimental studies are complemented by density functional theory calculations, proving that the pyrene unit is more active for H2 O2 production than the bipyridine and (diarylamino)benzene units reported previously. H2 O2 decomposition experiments verified that the distribution of pyrene units over a large surface area of COFs plays an important role in catalytic performance. The Py-Py-COF though contains more pyrene units than other COFs which induces a high H2 O2 decomposition due to a dense concentration of pyrene in close proximity over a limited surface area. Therefore, a two-phase reaction system (water-benzyl alcohol) was employed to inhibit H2 O2 decomposition. This is the first report on applying pyrene-based COFs in a two-phase system for photocatalytic H2 O2 generation.

Targeting aloe active compounds to c-KIT promoter G-quadruplex and comparative study of their anti proliferative property.

Small molecules targeting G-quadruplex of oncogene promoter is considered as a promising anticancer therapeutics approach. Natural aloe compounds aloe emodin, and its glycoside derivative aloe emodin-8-glucoside and aloin have anticancer activity and also have potential DNA binding ability. These three compounds have promising binding ability towards quadruplex structures particularly c-KIT G-quadruplex. Here, this study demonstrates complete biophysical study of these compounds to c-KIT quadruplex structure. Aloe emodin showed highest binding stabilization with c-KIT which has been proved by absorbance, fluorescence, dye displacement, ITC and SPR studies. Moreover, comparative study of these compounds with HCT 116 cells line also agreed to their anti proliferative property which may be helpful to establish these aloe compounds as potential anticancer drugs. This study comprises a complete biophysical study along with their anti proliferative property and demonstrates aloe emodin as a potent c-KIT binding molecule.

Cleavage of Abasic Sites in DNA by an Aminoquinoxaline Compound: Augmented Cytotoxicity and DNA Damage in Combination with an Anticancer Drug Chlorambucil in Human Colorectal Carcinoma Cells.

The elevated level of endogenous oxidative DNA damage and spontaneous deamination of DNA bases in cancer cells substantially increase the abasic sites in DNA via base excision repairs (BERs). Thus, the predominant BER pathway is a favorable target for cancer therapy. Interestingly, elevated levels of glutathione (GSH) in certain cancer cells, such as colon cancer, are associated with acquired resistance to several chemotherapeutic agents, which increase the difficulty for the treatment of cancer. Here, we have reported an ideal nitro group-containing monoquinoxaline DNA intercalator (1d), which is reduced into a fluorescent quinoxaline amine (1e) in the presence of GSH; concurrently, 1e (∼100 nM concentration) selectively causes the in vitro cleavage of abasic sites in DNA. 1e also binds to the tetrahydrofuran analogue of the abasic site in the nanomolar to low micromolar range depending on the nucleotide sequence opposite to the abasic site and also induces a structural change in abasic DNA. Furthermore, the amine compound (1e) augments the response of the specific bifunctional alkylating drug chlorambucil at a much lower concentration in the human colorectal carcinoma cell (HCT-116), and their combination shows a potential strategy for targeted therapy. Alone or in combination, 1d and 1e lead to a cascade of cellular events such as induction of DNA double-stranded breaks and cell arrest at G0/G1 and G2/M phases, eventually leading to apoptotic cell death in HCT-116 cells. Hence, the outcome of this study provides a definitive approach that will help optimize the therapeutic applications for targeting the abasic site in cancer cells.

A physicochemical introspection of porous organic polymer photocatalysts for wastewater treatment.

Over the past decade, porous organic polymers (POPs) have emerged as powerful photocatalysts for organic transformations and wastewater decontamination. The surface properties and pore space of POPs have been tailored to find optimal physical dimensions for adsorption and catalysis, whereas playing with the donor-acceptor building units lends them unique prospects for bandgap engineering, beneficial for customized applications including the degradation of simple as well as persistent pollutants. Here in this critical perspective, we focused beyond these generic scenarios and provided a detailed physicochemical explanation for the experimental observations. Considering the invaluable role of excitons, along with mobile electrons and holes, we fundamentally justified the reactivities of POPs with regard to water treatment. Both semiconducting and molecular catalyst approaches have been considered for different types of POPs. Depending on the porosity, structural formation and defects in the POP backbone, the exciton formation, charge separation, charge diffusion, etc. are critically explained, highlighting the influence of the dielectric constant and skeletal polarizability of the material. The translation of this fundamental understanding to various reactive oxygen species generation through charge transfer (e.g., O2˙-) and exciton-exciton annihilation (e.g., 1O2) by proximity-induced FRET or Dexter pathways is discussed. The role of the hydrophilic POP skeleton in overall in-water photochemical applications is also discussed. Finally, the gaps in the current state-of-the-art are considered and the future prospects to mitigate these issues are argued.

Substituent effect of benzyl moiety in nitroquinoxaline small molecules upon DNA binding: Cumulative destacking of DNA nucleobases leading to histone eviction.

Cooperative disruption of Watson-Crick hydrogen bonds, as well as base-destacking, is shown to be triggered by a quinoxaline-based small molecule consisting of an N,N-dimethylaminopropyl tether, and a para-substituted benzyl moiety. This events lead to superstructure formation and DNA condensation as evident from biophysical experiments and classical molecular dynamics simulations. The DNA superstructure formation by mono-quinoxaline derivatives is highly entropically favored and predominantly driven by hydrophobic interactions. Furthermore, oversupercoiling of DNA and base-destacking cumulatively induces histone eviction from in-vitro assembled nucleosomes at lower micromolar concentrations implicating biological relevance. The DNA structural modulation and histone eviction capacity of the benzyl para-substituents are in the order: -I > -CF3> -Br > -Me > -OMe > -OH, which is largely guided by the polarity of benzyl para-substituent and the resulting molecular topology. The most hydrophobic derivative 3c with para-iodo benzyl moiety causes maximal disruption of base pairing and generation of superstructures. Both these events gradually diminish as the polarity of the benzyl para-substituent increases. On the other hand, quinoxaline derivatives having heterocyclic ring instead of benzyl ring, or in the absence of N,N-dimethylamino head-group, is incapable of inducing any DNA structural change and histone eviction. Further, the quinoxaline compounds displayed potent anticancer activities against different cancer cell lines which directly correlates with the hydrophobic effects of the benzyl para-substituents. Overall, the present study provides new insights into the mechanistic approach of DNA structural modulation driven histone eviction guided by the hydrophobicity of synthesized compounds leading to cellular cytotoxicity towards cancer cells.

Novel rapid room temperature synthesis of conjugated microporous polymer for metal-free photocatalytic degradation of fluoroquinolones.

The existence of Fluoroquinolones (FQs), non-biodegradable pharmacophores, in the natural environment possesses a serious threat. We herein report a novel, rapid, room-temperature synthesis of semiconducting conjugated microporous polymer (CMP) for the decontamination of four second-generation FQs, Norfloxacin, Enrofloxacin, Ciprofloxacin, and Ofloxacin. The CMP demonstrated impressive gas uptake and FQ adsorption ability. Decreased HOMO-LUMO bandgap resulted in enhanced exciton pair generation on visible-light-illumination. Additionally, a high degree of photocurrent response and suitable redox potentials of the material conjointly endorsed its almost quantitative FQ-degradation efficiency. Ofloxacin showed the best removal efficiency with 0.061 and 0.207 min-1 adsorption and degradation rate constants, respectively, one of the highest values reported. The CMP exhibited equipotent activity for other FQs as well. On increasing the concentration of the FQs or decreasing the incident photo-intensity, quantitative removal efficiencies are observed. Changing the pH of the medium from acidic to alkaline did not impart any change in catalytic activity as well. The reactive species involved viz. O2-, 1O2, etc. and their roles in the degradation process were determined through control and trapping experiments. A plausible in-depth mechanistic pathway was assessed from the FQ degradation intermediates, and the reactive catalytic species substantiating step-by-step break down of the antibiotic backbone.

Quinoxaline derivatives disrupt the base stacking of hepatitis C virus-internal ribosome entry site RNA: reduce translation and replication.

RNA-biased small molecules with a monoquinoxaline core target the L-shaped structure of subdomain IIa of Hepatitis C virus internal ribosome entry site (IRES) RNA in proximity to the Mg2+ binding site. The binding event leads to the destacking of RNA bases, resulting in the inhibition of IRES-mediated translation and HCV RNA replication.

DNA Structural Alteration Leading to Antibacterial Properties of 6-Nitroquinoxaline Derivatives.

Structural integrity of the bacterial genome plays an important role in bacterial survival. Cellular consequences of an intolerable amount of change in the DNA structure are not well understood in bacteria. Here we have stated that binding of synthetic 6-nitroquinoxaline derivatives with DNA led to change in its global structure, subsequently culminating with over-supercoiled form through in-path intermediates. This structural change results in induction of programmed cell death like physiological hallmarks, which is dependent on substitution driven structural modulation properties of the scaffold. A sublethal dose of a representative derivative, 3a, significantly inhibits DNA synthesis, produces fragmented nucleoids, and alters membrane architecture. We have also shown that exposure to the compound changes the native morphology of Staphylococcus aureus cells and significantly disrupts preformed biofilms. Thus, our study gives new insight into bacterial responses to local or global DNA structural changes induced by 6-nitroquinoxaline small molecules.

Dataset on the development of palladium nanoparticle decorated colloidal porous organic polymer for photocatalytic Suzuki coupling.

Herein, we report the synthesis and characterization data of visible-light-active colloidal azobenzene-based porous organic polymer (Azo-POP) and its Pd-nanoparticle loaded analog (Pd-Azo-POP). The setup for photocatalytic Suzuki reactions triggered by Pd-Azo-POP under conventional batch reaction mode as well as in a prototypal continuous flow system has also been provided in addition to the detailed catalytic data including 1H and 13C NMR spectra of the obtained products. For further discussions on the materials, their effect on overall catalysis and mechanistic insight, please refer to the associated article "Pd-nanoparticle decorated azobenzene-based colloidal porous organic polymer for visible and natural sunlight-induced Mott-Schottky junction mediated instantaneous Suzuki coupling" (Chakraborty et al., 2019).

Intercalator-Induced DNA Superstructure Formation: Doxorubicin and a Synthetic Quinoxaline Derivative.

Small molecules that intercalate DNA have tremendous therapeutic potential. Typically, DNA intercalators do not alter the overall DNA double-helical structure, except locally at the intercalation sites. In a previous report, we showed that a quinoxaline-based intercalator with a mandatory benzyl substitution (1d) induced an unusually large circular dichroism signal upon DNA binding, suggesting the formation of intercalated DNA superstructures. However, no detailed structural studies have been reported. Using atomic force microscopy, we have probed the nature of the superstructure and report the formation of a plectonemically oversupercoiled structure of pBR322 plasmid DNA by 1d, where close association of distant DNA double-helical stretches is the predominant motif. Without the benzyl moiety (1a), no such DNA superstructure was observed. Similar superstructures were also observed with doxorubicin (dox), a therapeutically important DNA intercalator, suggesting that the superstructure is common to some intercalators. The superstructure formation, for both intercalators, was observed to be GC-specific. Interestingly, at higher concentrations (1d and dox), the DNA superstructure led to DNA condensation, a phenomenon typically associated with polyamines but not intercalators. The superstructure may have important biological relevance in connection to a recent study in which dox was shown to evict histone at micromolar concentrations.

Synthesis and characterization of chitosan-based waterborne polyurethane for textile finishes.

Chitosan has gained an increased interest of researchers due to its nontoxic, biodegradable, biocompatible and renewable properties as well as its antimicrobial activity. In this work, a series of chitosan-based waterborne polyurethane (CS-WPU) emulsions were synthesized. The synthesis was accomplished by using a two-step emulsion polymerization process. The pre-polymer was prepared using hexamethylene diisocyanate (HDI) and polyethylene glycol (PEG; MW = 6 kDa). Afterwards, the chain extension step was performed by using different mole ratios of chitosan. Moreover, the effect of chitosan on physicochemical properties of the emulsion was studied. To evaluate textile performances such as tear strength, tensile strength and pilling, the CS-WPU emulsion was applied on different plain weave polyester cotton dyed and printed fabrics by using pad-dry cure techniques. The antimicrobial activity of the treated and untreated fabrics was also evaluated via the agar diffusion method. The results displayed that incorporation of chitosan has prominent effects on tensile tear strength, tear strength and antimicrobial activity of polyester cotton dyed and printed fabrics. Moreover, antimicrobial activity was considerably enhanced as the mole ratio of the chitosan was increased. The results emphasize that CS-WPU based on HDI exhibits a better performance as compared to IPDI.

Metal organic frameworks mimicking natural enzymes: a structural and functional analogy.

In this review, we have portrayed the structure, synthesis and applications of a variety of biomimetic MOFs from an unprecedented angle. Synthetic MOF analogues of five distinct enzymes: phosphotriesterase, hydrogenase, cytochrome P450, chymotrypsin and carbonic anhydrase, have been discussed with their skeletal comparison to actual enzymatic active sites as reference, and an explanation of catalytic pathways from the mechanistic cycle of the corresponding enzymes is depicted. We demonstrated critically each of the five discrete situations by assimilating available benchmark researches in an attempt to provide a concise literature source on the ingenious design strategies and versatile biomimetic applications of this domain of materials.