Probing the Human Estrogen Receptor-α Binding Requirements for Phenolic Mono- and Di-Hydroxyl Compounds: A Combined Synthesis, Binding and Docking Study

Various estrogen analogs were synthesized and tested for binding to human ERα using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di-hydroxyl compounds sometimes bind in two orientations, which are flipped in terms of relative positioning of their hydroxyl groups. Di-hydroxyl compounds were predicted to bind with their aliphatic hydroxyl group interacting with His524 in ERα. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERβ over ERα, and was also 25-fold specific for agonist ERβ versus antagonist activity. Docking predictions suggest this specificity may be due to interaction of the aliphatic hydroxyl with His475 in the agonist form of ERβ, versus with Thr299 in the antagonist form. But, the presence of this aliphatic hydroxyl is not required in all compounds, since mono-hydroxyl (phenolic) compounds bind ERα with high affinity, via hydroxyl hydrogen bonding interactions with the ERα Arg394/Glu353/water triad, and van der Waals interactions with the rest of the molecule

Conjugated poly-ynes and poly(metalla-ynes) incorporating thiophene-based spacers for solar cell (SC) applications

Solar cells (SCs) are of considerable current research interest because of their potential as a clean alternative to fossil fuels. Researchers across the globe are developing novel polymeric materials with enhanced power conversion efficiency (PCE). Conjugated poly-ynes and poly(metalla-ynes) incorporating late transition metals and thiophene-based spacers have played a very important role in this strategic area of materials research. The performance of the SCs can be optimized by varying the conjugated spacers and/or the metal ions along the polymer backbone. Therefore, an analysis of structure-photovoltaic property relationships in poly-ynes and poly(metalla-ynes) is desirable as a guide for the development of new functional materials for use in SCs. Keeping the importance of this strategic topic in mind, herein we present a brief review on conjugated poly-ynes and poly(metalla-ynes) incorporating thiophene-based spacers that have potential SC applications. Attempts have been made to correlate the photovoltaic performance of the SCs to the chemical structure of thiophene-incorporated poly-ynes and poly(metalla-ynes). The performance of SCs is also strongly influenced by other factors such as morphology and device structure.</p

Spectral Data for Probing the human estrogen receptor-alpha binding requirements for phenolic mono- and do-hydroxyl compounds: A combined synthesis, binding and docking study

Spectral data used in the course of researching Probing the human estrogen receptor-alpha binding requirements for phenolic mono- and do-hydroxyl compounds: A combined synthesis, binding and docking study . Various estrogen analogs were synthesized and tested for binding to human ERα using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di-hydroxyl compounds sometimes bind in two orientations, which are flipped in terms of relative positioning of their hydroxyl groups. Di-hydroxyl compounds were predicted to bind with their aliphatic hydroxyl group interacting with His524 in ERα. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERβ over ERα, and was also 25-fold specific for agonist ERβ versus antagonist activity. Docking predictions suggest this specificity may be due to interaction of the aliphatic hydroxyl with His475 in the agonist form of ERβ, versus with Thr299 in the antagonist form. But, the presence of this aliphatic hydroxyl is not required in all compounds, since mono-hydroxyl (phenolic) compounds bind ERα with high affinity, via hydroxyl hydrogen bonding interactions with the ERα Arg394/Glu353/water triad, and van der Waals interactions with the rest of the molecule

Sudden Cardiac Death in Patients Under 49 Years Including Adolescents: A single-centre study from Oman

Objectives: This study aimed to identify the incidence of sudden cardiac death (SCD0 in adult patients under the age of 49 years, including adolescents with an out-of-hospital cardiac arrest that presented to the emergency department of a tertiary care hospital. Methods: This retrospective cross-sectional study was conducted at the Royal Hospital, Muscat, Oman, between January 2015 and December 2019. All patients with out-of-hospital cardiac arrest were enrolled. The incidence of SCD was evaluated. Information about the patient's demographic data, the site of cardiac arrest, the mode of arrival, the duration of pre-arrest symptoms and if cardiopulmonary resuscitation was performed was gathered. Survival data at 3-year follow-up was obtained. Results: A total of 117 out of 769 (15%) patients met the criteria for SCD. Male gender was predominant, with a median age of 33 years. In about 79.5% of the patients, cardiac arrest was witnessed. Only 43 patients (36.8%) received cardiopulmonary resuscitation at the arrest site; 21 patients (17.9%) had a shockable rhythm and 96 patients (82.1%) had a non-shockable rhythm. Spontaneous circulation was returned in 15 patients (12.8%). Nine patients (7.7%) were discharged from the hospital and 8 (6.8%) survived at least 36 months. Conclusion: The study findings indicate the prevalence of SCD among patients who experienced a cardiac arrest outside the hospital. Unfortunately, only a small number of patients were able to survive in the long term. By implementing preemptive screening for individuals and their families, it may be possible to prevent SCD and improve outcomes for those affected. Keywords: Death, Sudden, Cardiac; Epidemiology; Etiology; Risk Factors; Incidence; Cardiopulmonary Resuscitation; Retrospective Studies; Oman

Probing the Human Estrogen Receptor-Alpha Binding Requirements for Phenolic Mono- and di-Hydroxyl compounds: A Combined Synthesis, Binding and Docking Study

Various estrogen analogs were synthesized and tested for binding to human ERα using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di-hydroxyl compounds sometimes bind in two orientations, which are flipped in terms of relative positioning of their hydroxyl groups. Di-hydroxyl compounds were predicted to bind with their aliphatic hydroxyl group interacting with His524 in ERα. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERβ over ERα, and was also 25-fold specific for agonist ERβ versus antagonist activity. Docking predictions suggest this specificity may be due to interaction of the aliphatic hydroxyl with His475 in the agonist form of ERβ, versus with Thr299 in the antagonist form. But, the presence of this aliphatic hydroxyl is not required in all compounds, since mono-hydroxyl (phenolic) compounds bind ERα with high affinity, via hydroxyl hydrogen bonding interactions with the ERα Arg394/Glu353/water triad, and van der Waals interactions with the rest of the molecule

Conjugated poly-ynes and poly(metalla-ynes) incorporating thiophene-based spacers for solar cell (SC) applications

Solar cells (SCs) are of considerable current research interest because of their potential as a clean alternative to fossil fuels. Researchers across the globe are developing novel polymeric materials with enhanced power conversion efficiency (PCE). Conjugated poly-ynes and poly(metalla-ynes) incorporating late transition metals and thiophene-based spacers have played a very important role in this strategic area of materials research. The performance of the SCs can be optimized by varying the conjugated spacers and/or the metal ions along the polymer backbone. Therefore, an analysis of structure-photovoltaic property relationships in poly-ynes and poly(metalla-ynes) is desirable as a guide for the development of new functional materials for use in SCs. Keeping the importance of this strategic topic in mind, herein we present a brief review on conjugated poly-ynes and poly(metalla-ynes) incorporating thiophene-based spacers that have potential SC applications. Attempts have been made to correlate the photovoltaic performance of the SCs to the chemical structure of thiophene-incorporated poly-ynes and poly(metalla-ynes). The performance of SCs is also strongly influenced by other factors such as morphology and device structure.</p

The impact of the alkyne substitution pattern and metalation on the photo-isomerization of azobenzene-based platinum(II) diynes and polyynes

Trimethylsilyl-protected dialkynes incorporating azobenzene linker groups, Me₃SiCCRCCSiMe₃ (R = azobenzene-3,3′-diyl, azobenzene-4,4′-diyl, 2,5-dioctylazobenzene-4,4′-diyl), and the corresponding terminal dialkynes, HCCRCCH, have been synthesized and characterized. The CuI-catalyzed dehydrohalogenation reaction between <i>trans</i>-[Ph­(Et₃P)₂PtCl] and the deprotected dialkynes in a 2:1 ratio in ⁱPr₂NH/CH₂Cl₂ gives the platinum­(II) diynes <i>trans</i>-[Ph­(Et₃P)₂PtCCRCCPt­(PEt₃)₂Ph], while the dehydrohalogenation polycondensation reaction between <i>trans</i>-[(ⁿBu₃P)₂PtCl₂] and the dialkynes in a 1:1 molar ratio under similar reaction conditions affords the platinum­(II) polyynes, [−Pt­(PⁿBu₃)₂–CCRCC−]_<i>n</i>. The materials have been characterized spectroscopically, with the diynes also studied using single-crystal X-ray diffraction. The platinum­(II) diynes and polyynes are all soluble in common organic solvents. Optical-absorption measurements show that the compounds incorporating the <i>para</i>-alkynylazobenzene spacers have a higher degree of electronic delocalisation than their <i>meta</i>-alkynylazobenzene counterparts. Reversible photoisomerization in solution was observed spectroscopically for the alkynyl-functionalized azobenzene ligands and, to a lesser extent, for the platinum­(II) complexes. Complementary quantum-chemical modeling was also used to analyze the optical properties and isomerization energetics

Genome-wide inference of regulatory networks in Streptomyces coelicolor

Background: The onset of antibiotics production in Streptomyces species is co-ordinated with differentiation events. An understanding of the genetic circuits that regulate these coupled biological phenomena is essential to discover and engineer the pharmacologically important natural products made by these species. The availability of genomic tools and access to a large warehouse of transcriptome data for the model organism, Streptomyces coelicolor, provides incentive to decipher the intricacies of the regulatory cascades and develop biologically meaningful hypotheses. Results: In this study, more than 500 samples of genome-wide temporal transcriptome data, comprising wild-type and more than 25 regulatory gene mutants of Streptomyces coelicolor probed across multiple stress and medium conditions, were investigated. Information based on transcript and functional similarity was used to update a previously-predicted whole-genome operon map and further applied to predict transcriptional networks constituting modules enriched in diverse functions such as secondary metabolism, and sigma factor. The predicted network displays a scale-free architecture with a small-world property observed in many biological networks. The networks were further investigated to identify functionally-relevant modules that exhibit functional coherence and a consensus motif in the promoter elements indicative of DNA-binding elements. Conclusions: Despite the enormous experimental as well as computational challenges, a systems approach for integrating diverse genome-scale datasets to elucidate complex regulatory networks is beginning to emerge. We present an integrated analysis of transcriptome data and genomic features to refine a whole-genome operon map and to construct regulatory networks at the cistron level in Streptomyces coelicolor. The functionally-relevant modules identified in this study pose as potential targets for further studies and verification.

Dicopper(I) Complexes Incorporating Acetylide-functionalized Pyridinyl-based Ligands::Synthesis, Structural and Photovoltaic Studies

Heteroaryl incorporated acetylide-functionalized pyridinyl ligands (<b>L1–L6</b>) with the general formula Py-CC-Ar (Py = pyridine and Ar = <i>thiophene-2-yl</i>, 2,2′<i>-bithiophene]-5-yl</i>, 2,2′<i>:5</i>′,2″<i>-terthiophene]-5-yl</i>, <i>thieno­[2,3-<i>b</i>]­thiophen-2-yl</i>, <i>quinoline-5-yl</i>, <i>benzo­[c]­[1,2,5]­thiadiazole-5-yl</i>) have been synthesized by Pd(0)/Cu­(I)-catalyzed cross-coupling reaction of 4-ethynylpyridine and the respective heteroaryl halide. Ligands <b>L1–L6</b> were isolated in respectable yields and characterized by microanalysis, IR spectroscopy, ¹H NMR spectroscopy, and ESI-MS mass spectrometry. A series of dinuclear Cu­(I) complexes <b>1</b>–<b>10</b> have been synthesized by reacting <b>L1–L6</b> with CuI and triphenylphosphine (PPh₃) (<b>R1</b>) or with an anchored phosphine derivative, 4-(diphenylphosphino) benzoic acid (<b>R2</b>)/2-(diphenylphosphino)­benzenesulfonic acid (<b>R3</b>), in a stoichiometric ratio. The complexes are soluble in common organic solvents and have been characterized by analytical, spectroscopic, and computational methods. Single-crystal X-ray structure analysis confirmed rhomboid dimeric structures for complexes <b>1</b>, <b>2</b>, <b>4</b>, and <b>5</b>, and a polymeric structure for <b>6</b>. Complexes <b>1</b>–<b>6</b> showed oxidation potential responses close to 0.9 V vs Fc^0/+, which were chemically irreversible and are likely to be associated with multiple steps and core oxidation. Preliminary photovoltaic (PV) results of these new materials indicated moderate power conversion efficiency (PCE) in the range of 0.15–1.56% in dye-sensitized solar cells (DSSCs). The highest PCE was achieved with complex <b>10</b> bearing the sulfonic acid anchoring functionality

Metabolic and evolutionary insights into the closely-related species Streptomyces coelicolor and Streptomyces lividans deduced from high-resolution comparative genomic hybridization

Whilst being closely related to the model actinomycete Streptomyces coelicolor A3(2), S. lividans 66 differs from it in several significant and phenotypically observable ways, including antibiotic production. Previous comparative gene hybridization studies investigating such differences have used low-density (one probe per gene) PCR-based spotted arrays. Here we use new experimentally optimised 104,000 × 60-mer probe arrays to characterize in detail the genomic differences between wild-type S. lividans 66, a derivative industrial strain, TK24, and S. coelicolor M145