Enhancing the Spin–Orbit Coupling in Fe3O4 Epitaxial Thin Films by Interface Engineering

10.1021/acsami.6b0947884027353-2735

Drug and Cell Type-Specific Regulation of Genes with Different Classes of Estrogen Receptor β-Selective Agonists

Estrogens produce biological effects by interacting with two estrogen receptors, ERα and ERβ. Drugs that selectively target ERα or ERβ might be safer for conditions that have been traditionally treated with non-selective estrogens. Several synthetic and natural ERβ-selective compounds have been identified. One class of ERβ-selective agonists is represented by ERB-041 (WAY-202041) which binds to ERβ much greater than ERα. A second class of ERβ-selective agonists derived from plants include MF101, nyasol and liquiritigenin that bind similarly to both ERs, but only activate transcription with ERβ. Diarylpropionitrile represents a third class of ERβ-selective compounds because its selectivity is due to a combination of greater binding to ERβ and transcriptional activity. However, it is unclear if these three classes of ERβ-selective compounds produce similar biological activities. The goals of these studies were to determine the relative ERβ selectivity and pattern of gene expression of these three classes of ERβ-selective compounds compared to estradiol (E2), which is a non-selective ER agonist. U2OS cells stably transfected with ERα or ERβ were treated with E2 or the ERβ-selective compounds for 6 h. Microarray data demonstrated that ERB-041, MF101 and liquiritigenin were the most ERβ-selective agonists compared to estradiol, followed by nyasol and then diarylpropionitrile. FRET analysis showed that all compounds induced a similar conformation of ERβ, which is consistent with the finding that most genes regulated by the ERβ-selective compounds were similar to each other and E2. However, there were some classes of genes differentially regulated by the ERβ agonists and E2. Two ERβ-selective compounds, MF101 and liquiritigenin had cell type-specific effects as they regulated different genes in HeLa, Caco-2 and Ishikawa cell lines expressing ERβ. Our gene profiling studies demonstrate that while most of the genes were commonly regulated by ERβ-selective agonists and E2, there were some genes regulated that were distinct from each other and E2, suggesting that different ERβ-selective agonists might produce distinct biological and clinical effects

Quantitative assessment of hit detection and confirmation in single and duplicate high-throughput screenings.

The process of identifying active targets (hits) in high-throughput screening (HTS) usually involves 2 steps: first, removing or adjusting for systematic variation in the measurement process so that extreme values represent strong biological activity instead of systematic biases such as plate effect or edge effect and, second, choosing a meaningful cutoff on the calculated statistic to declare positive compounds. Both false-positive and false-negative errors are inevitable in this process. Common control or estimation of error rates is often based on an assumption of normal distribution of the noise. The error rates in hit detection, especially false-negative rates, are hard to verify because in most assays, only compounds selected in primary screening are followed up in confirmation experiments. In this article, the authors take advantage of a quantitative HTS experiment in which all compounds are tested 42 times over a wide range of 14 concentrations so true positives can be found through a dose-response curve. Using the activity status defined by dose curve, the authors analyzed the effect of various data-processing procedures on the sensitivity and specificity of hit detection, the control of error rate, and hit confirmation. A new summary score is proposed and demonstrated to perform well in hit detection and useful in confirmation rate estimation. In general, adjusting for positional effects is beneficial, but a robust test can prevent overadjustment. Error rates estimated based on normal assumption do not agree with actual error rates, for the tails of noise distribution deviate from normal distribution. However, false discovery rate based on empirically estimated null distribution is very close to observed false discovery proportion

Odd-electron-bonded sulfur radical cations: X-ray structural evidence of a sulfur-sulfur three-electron σ-bond

The one-electron oxidations of 1,8-chalcogen naphthalenes Nap(SPh)2 (1) and Nap(SPh)(SePh) (2) lead to the formation of persistent radical cations 1•+ and 2•+ in solution. EPR spectra, UV-vis absorptions, and DFT calculations show a three-electron σ-bond in both cations. The former cation remains stable in the solid state, while the latter dimerizes upon crystallization and returns to being radical cations upon dissolution. This work provides conclusive structural evidence of a sulfur-sulfur three-electron σ-bond (in 1•+) and a rare example of a persistent heteroatomic three-electron σ-bond (in 2•+)

A crystalline phosphaalkene radical anion

Salts containing phosphaalkene radical anions have been isolated and characterized by electron paramagnetic resonance (EPR) spectroscopy, UV-vis absorption spectroscopy, and single-crystal X-ray diffraction. The radical anions feature elongated P-C bonds and an aromatization of fulvene compared to the neutral phosphaalkene. Their EPR spectra and theoretical calculations indicate the spin density of the radicals mainly resides on phosphorus atoms. This work provides the first example of a crystalline phosphaalkene radical anion. 2014 American Chemical Society

Nitrogen analogues of Thiele\u27s hydrocarbon

A series of bis[N,N-di-(4-methoxylphenyl)amino]arene dications 12+-32+ have been synthesized and characterized. Their electronic structures were investigated by various experiments assisted by theoretical calculations. It was found that they are singlets in the ground state and that their diradical character is dependent on the bridging moiety. 32+ has a smaller singlet-triplet energy gap and its excited triplet state is thermally readily accessible. The work provides a nitrogen analogue of Thiele\u27s hydrocarbon with considerable diradical character

Two stable phosphorus-containing four-membered ring radical cations with inverse spin density distributions

Two phosphorus-containing four-membered ring radical cations 1 •+ and 2•+ have been isolated and characterized by UV-vis absorption spectroscopy, electron paramagnetic resonance (EPR), and single-crystal X-ray diffraction. Compared with neutral molecules 1 and 2, radical 1•+ has elongated P-P bonds and more pyramidalized phosphorus atoms, while shortened P-Nring distances and larger angles around phosphorus centers are observed for 2•+. EPR studies indicate that for 1•+ spin density mainly resides on the exocyclic nitrogen atoms with very minor contribution from endocyclic phosphorus atoms, while the situation is opposite for 2•+. Such an inverse spin density distribution is controlled by the exocyclic substituents, which is supported by DFT calculations

Access to stable metalloradical cations with unsupported and isomeric metal-metal hemi-bonds

Metalloradical species [Co2Fv(CO)4].+ (1.+, Fv=fulvalenediyl) and [Co2Cp2(CO)4].+ (2.+, Cp=η5-C5H5), formed by one-electron oxidations of piano-stool cobalt carbonyl complexes, can be stabilized with weakly coordinating polyfluoroaluminate anions in the solid state. They feature a supported and an unsupported (i.e. unbridged) cobalt-cobalt three-electron σ bond, respectively, each with a formal bond order of 0.5 (hemi-bond). When Cp is replaced by bulkier Cp∗ (Cp∗=η5-C5Me5), an interchange between an unsupported radical [Co2Cp∗2(CO)4].+ (anti-3.+) and a supported radical [Co2Cp∗2(μ-CO)2(CO)2].+ (trans-3.+) is observed in solution, which cocrystallize and exist in the crystal phase. 2.+ and anti-3.+ are the first stable thus isolable examples that feature an unsupported metal-metal hemi-bond, and the coexistence of anti-3.+ and trans-3.+ in one crystal is unprecedented in the field of dinuclear metalloradical chemistry. The work suggests that more stable metalloradicals of metal-metal hemi-bonds may be accessible by using metal carbonyls together with large and weakly coordinating polyfluoroaluminate anions