Phenyl-containing Compounds Research Articles

PM2.5 exposure contributes to anxiety and depression-like behaviors via phenyl-containing compounds interfering with dopamine receptor

As a global problem, fine particulate matter (PM2.5) really needs local fixes. Considering the increasing epidemiological relevance to anxiety and depression but inconsistent toxicological results, the most important question is to clarify whether and how PM2.5 causally contributes to these mental disorders and which components are the most dangerous for crucial mitigation in a particular place. In the present study, we chronically subjected male mice to a real-world PM2.5 exposure system throughout the winter heating period in a coal combustion area and revealed that PM2.5 caused anxiety and depression-like behaviors in adults such as restricted activity, diminished exploratory interest, enhanced repetitive stereotypy, and elevated acquired immobility, through behavioral tests including open field, elevated plus maze, marble-burying, and forced swimming tests. Importantly, we found that dopamine signaling was perturbed using mRNA transcriptional profile and bioinformatics analysis, with Drd1 as a potential target. Subsequently, we developed the Drd1 expression-directed multifraction isolating and nontarget identifying framework and identified a total of 209 compounds in PM2.5 organic extracts capable of reducing Drd1 expression. Furthermore, by applying hierarchical characteristic fragment analysis and molecular docking and dynamics simulation, we clarified that phenyl-containing compounds competitively bound to DRD1 and interfered with dopamine signaling, thereby contributing to mental disorders. Taken together, this work provides experimental evidence for researchers and clinicians to identify hazardous factors in PM2.5 and prevent adverse health outcomes and for local governments and municipalities to control source emissions for diminishing specific disease burdens.

Color characteristics and pyrolysis volatile properties of main colored fractions from the Maillard reaction models of glucose with three amino acids

The effects of hydrosoluble colored fractions generated in the Maillard reaction models on the volatiles of pyrolytic Maillard reaction products was investigated. The hydrosoluble colored fractions obtained by reaction of glucose with glycine (Gly-Glc), proline (Pro-Glc) and phenylalanine (Phe-Glc) respectively at 125 °C were separated using Sephadex LH-20 Gel column. The colored fraction with large molecular weight had a higher contribution to the overall color and more glucose residue structures in main skeleton than that with small molecular weight in the same model. Gel permeation chromatography analysis indicated that these colored fractions had continuous relative molecular weight distribution (1000–80000 Da). Pyrolysis - gas chromatography - mass spectrometry determination (pyrolysis temperature: 160∼900 °C) suggested that furans and pyrroles were the main volatiles of two Gly-Glc fractions after pyrolysis, and the key pyrolysis volatiles of Pro-Glc fraction were furans, pyrroles, pyran, indole and cyclopentenes, which gave a freshly baked bread, nutty, coffee-like and sweet caramel-like odor. Especially phenyl-containing compounds seemed typical indicators of Phe-Glc fraction pyrolysis products, exhibiting a benzene-like, tallowy, sweet, balsamic and floral odor. The hydrosoluble colored fractions produced by different Maillard reactions had different pyrolytic volatile properties and were suitable for the development of bakery food improver with different color and flavor requirements.

Superatomic Ag58 nanoclusters incorporating a [MS4@Ag12]2+ (M = Mo or W) kernel show aggregation-induced emission

In core-shell silver nanoclusters, the control of core structure presents a more formidable challenge compared to that of the shell structure. Here, we report the successful synthesis and characterization of four distinct silver thiolate nanoclusters [MS4@Ag12@Ag46S24(dppb)12] (M = Mo or W), each incorporating a cup-like [MS4@Ag12]2+ kernel. These nanoclusters were meticulously prepared using (NH4)2MoS4 or (NH4)2WS4 as both a template and a controlled source of S2− ions. Remarkably, we have observed a unique configuration within these eight-electron superatomic Ag58 nanoclusters, where the zero-valent Ag atoms reside exclusively within the inner [MS4@Ag12]2+ kernel. This stands in contrast to other superatomic clusters possessing an Ag(0) core. Notably, the introduction of phenyl-containing compounds during the synthesis process induced a transformation in the space group symmetry from C2/c to I4¯. This transformative effect was found to originate from the interplay between adjacent 1,4-bis(diphenylphosphino)butane (dppb) ligands, which facilitated enhanced emission through aggregation-induced intermolecular interactions, specifically C−H···π interactions. Collectively, our findings contribute substantively to the understanding of the intricate relationship between nanocluster structures and their corresponding properties, shedding light on the crucial roles played by templates and diphosphine ligands in this context.

Novel Benzylamine Derivatives: Synthesis, Anti-Mycobacterium Tuberculosis Evaluation and Predicted ADMET Properties

Background: Tuberculosis (TB), a disease caused by the bacillus bacteria Mycobacterium tuberculosis is one of the major contributors of ill health in the world. TB is ranked in the top 10 causes of death globally and it is the leading killer associated with a single infectious agent. According to the World Health Organization (WHO), global number of deaths associated with TB have been slowly declining with 1.3 million in reported 2016 and 2017, and 1.2 million reported in 2018 and 2019. Objective: The synthesis, characterisation, biological evaluations, and the prediction of ADMET properties of the novel benzylamine derivatives. Methods: Commercially available reagents and solvents were purchased from Sigma Aldrich and Merck (South Africa). All chemicals were used as received, unless otherwise stated. The synthesised crude compounds were purified by flash silica gel column chromatography (5 – 30% ethyl acetate in hexane). The successful formation and purity of the synthesised compounds was confirmed by NMR, HRMS and melting point. Results: The respective organic compounds were synthesised by treating 3-ethoxysalcyladehyde, 5-bromo-3-ethoxysalcyladehyde, 5-chloro-3-ethoxysalcyladehyde with various aromatic amines and the products were obtained in good to excellent yields. The 1H and 13C NMR spectra of all the products showed the appearance of the methylene signals ranging from 3.88 – 4.68 ppm and 42.25 – 52.57 ppm respectively. Additionally, most compounds showed anti-Mycobacterium tuberculosis activity that ranged between 20 and 28 µM. Conclusion: A total of 36 compounds were synthesised and successfully biologically evaluated against Mycobacterium tuberculosis (Mtb) H37RV strain. All compounds showed activity against Mtb at concentrations of > 20 µM < 28 µM with the exception of compound one that was active against Mtb at higher concentration (MIC90 > 125 µM).

The Power of Nonconventional Phenyl C–H···N Hydrogen Bonds: Supportive Crystal-Packing Force and Dominant Supramolecular Engineering Force

The role of phenyl C–H···N interactions in crystal engineering is explored with a variety of fluorinated phenyl-containing compounds. In particular, we show that this interaction can guide the formation of one-dimensional phenyl C–H···N hydrogen-bonded ribbons with, for example, 4-(2,3,5,6-tetrafluorophenylethynyl)pyridine. The interaction is shown to also control the formation of self-complementary homodimers with 3-(2,3,4,5-tetrafluorophenylethynyl)pyridine. We also demonstrate that the phenyl C–H···N hydrogen bond interaction is capable of enticing co-crystallization of molecules such as 2,3,5,6,2′,3′,5′,6′-octafluorobiphenyl and 4,4′-dipyridyl. Finally, we describe the use of an intramolecular scaffold to evaluate the effect of electron-withdrawing substituents on the strength of a phenyl C–H···N hydrogen bond.

Novel liquid-crystalline mesogens and main-chain chiral smectic thiol-ene polymers based on trifluoromethylphenyl moieties

The synthesis and characterization of a series of novel liquid-crystalline molecules containing a trifluoromethylphenyl core or a 2,3-bis(trifluoromethyl)phenyl core is described. All trifluoromethylphenyl-containing compounds (W530, W551, and W558) have mesomorphic properties while 2,3-bis(trifluoromethyl)phenyl-containing compounds (W555, W556, W557) are room-temperature crystals without mesophases. Thereafter, based on the chemical structure of W558, to pursue a mesogen with a large electroclinic effect in the SmA* phase for development into electromechanical actuators, a chiral smectic thiol-ene monomer (K0901) is synthesized and polymerized in organic solvents. The polymer is characterized by GPC, DSC, PLM, XRD and shows an expected I–SmA* –Glass phase sequence though the electroclinic effect is relatively small.

Water-soluble calix[4]resorcinarenes as chiral NMR solvating agents for phenyl-containing compounds

Water-soluble calix[4]resorcinarenes with 3- and 4-hydroxyproline substituent groups are evaluated as chiral NMR solvating agents on a series of monosubstituted phenyl-containing compounds. The substrates interact with the calixresorcinarene through insertion of the aromatic ring into the cavity. Cationic, anionic, and neutral substrates were examined, and all exhibited enantiomeric discrimination in the 1H NMR spectrum with one or more of the calixresorcinarenes. The hydroxyproline derivatives were almost always more effective at causing enantiodifferentiation than the corresponding proline derivative. Presumably the hydroxyl group on the proline moieties is involved in interactions with the substituent groups of the substrate that are important in creating chiral recognition. The enantiomeric discrimination in the 1H NMR spectrum is large enough to permit the analysis of enantiomeric purity.

Carboxymethylated cyclodextrins and their paramagnetic lanthanide complexes as water-soluble chiral NMR solvating agents

Cyclodextrins that are indiscriminately carboxymethylated at the 2-, 3-, and 6-position are used as chiral NMR solvating agents for cationic aromatic amines and aromatic hydroxy amines. Enantiomeric discrimination with the α-, β-, and γ-cyclodextrin derivatives is compared. The carboxymethylated derivatives are consistently more effective as chiral NMR discriminating agents for cationic substrates than native cyclodextrins. The most effective cyclodextrin varies for different substrates, although the β-cyclodextrin derivative is usually the best for the phenyl-containing compounds examined herein. Addition of paramagnetic praseodymium(III) or ytterbium(III) to mixtures of the carboxymethylated cyclodextrin and substrate often causes enhancements in enantiomeric discrimination and facilitates measurements of enantiomeric purity. The lanthanide ion bonds to the carboxymethyl groups and shifts the NMR spectra of substrate molecules in the cyclodextrin cavity.

Water‐Soluble Calix[4]resorcarenes as Enantioselective NMR Shift Reagents for Aromatic Compounds.

A tetra l-prolinylmethyl derivative of a tetra-sulfonated calix[4]resorcarene (1) is an effective chiral NMR solvating agent for water-soluble compounds with phenyl, pyridyl, bicyclic aromatic, or indole rings. These aromatic compounds form host−guest complexes with the calix[4]resorcarene in water. Complexation of substrates with the calix[4]resorcarene is likely promoted by hydrophobic effects, and bicyclic substrates have association constants with the calix[4]resorcarene larger than those of similar phenyl-containing compounds. Aromatic resonances of the substrates show substantial upfield shifts because of shielding from the aromatic rings of the calix[4]resorcarene, and several resonances in the 1H NMR spectra typically exhibit enantiomeric discrimination. The extent of enantiomeric discrimination depends in part on interactions of the substituent groups of the substrates with the prolinylmethyl groups of the calix[4]resorcarene. The effectiveness of a calix[4]resorcarene prepared from N-methyl-l-al...

Water-Soluble Calix[4]resorcarenes as Enantioselective NMR Shift Reagents for Aromatic Compounds

A tetra L-prolinylmethyl derivative of a tetra-sulfonated calix[4]resorcarene (1) is an effective chiral NMR solvating agent for water-soluble compounds with phenyl, pyridyl, bicyclic aromatic, or indole rings. These aromatic compounds form host-guest complexes with the calix[4]resorcarene in water. Complexation of substrates with the calix[4]resorcarene is likely promoted by hydrophobic effects, and bicyclic substrates have association constants with the calix[4]resorcarene larger than those of similar phenyl-containing compounds. Aromatic resonances of the substrates show substantial upfield shifts because of shielding from the aromatic rings of the calix[4]resorcarene, and several resonances in the 1H NMR spectra typically exhibit enantiomeric discrimination. The extent of enantiomeric discrimination depends in part on interactions of the substituent groups of the substrates with the prolinylmethyl groups of the calix[4]resorcarene. The effectiveness of a calix[4]resorcarene prepared from N-methyl-L-alanine (2) as a chiral NMR discriminating agent is compared to the L-prolinylmethyl derivative.

An Enantioselective NMR Shift Reagent for Cationic Aromatics

[structure: see text] The water-soluble tetra l-prolinylmethyl derivative of a tetrasulfonated calix[4]resorcarene is an effective chiral NMR solvating agent for compounds with bicyclic aromatic or indole rings. Complexation of bicyclic substrates with the calix[4]resorcarene is likely promoted by hydrophobic effects. The bicyclic substrates have larger association constants with the calix[4]resorcarene than similar phenyl-containing compounds. Substantial enantiomeric discrimination is observed for several resonances in the (1)H NMR spectra of these substrates.

Radical Cation Bond Cleavage Pathways for Naphthyl-Containing Coal Model Compounds

A series of naphthyl-containing compounds has been synthesized. The radical cations of these compounds were generated in solution using three independent techniques. These compounds were found to undergo bond cleavage reactions in exact analogy to the corresponding phenyl-containing compounds. The radical cations of these compounds were also generated in the gas phase in a mass spectrometer and show the same reactivity patterns as was observed in solution. Under coal liquefaction conditions, a different reactivity pattern of these compounds has been previously observed but ascribed to reactions of radical cations. Since the radical cations of naphthyl-containing model compounds react differently than the naphthyl-containing model compounds under coal liquefaction conditions, a reinterpretation of catalyst-initiated bond cleavage mechanics in naphthyl-containing coal model compounds should be untertaken

Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene D4 receptor antagonists. 4. Addition of chromone moiety enhances leukotriene D4 receptor binding affinity

The combination of the benzopyran-4-one ring, a moiety found in the prototype leukotriene antagonist, FPL 55,712, with the (2-quinolinylmethoxy)phenyl group led to a significant increase in leukotriene receptor binding affinity. This modification resulted in a 10,000-fold improvement in binding affinity compared to FPL 55,712. Compound 7 (RG 12553), with a Ki value of 0.1 nM, has higher affinity than the natural agonist LTD4 and is one of the most potent LTD4 antagonists reported. The structure-activity relationships of this series of potent leukotriene antagonists are discussed.

(2-Quinolinylmethoxy)phenyl-containing compounds as leukotriene receptor antagonists: A brief review of structure-activity relationships and the biological profile of RG 12525

(2-Quinolinylmethoxy)phenyl-containing compounds as leukotriene receptor antagonists: A brief review of structure-activity relationships and the biological profile of RG 12525

The development of a novel series of (quinolin-2-ylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 3. Structural variation of the acidic side chain to give antagonists of enhanced potency

This paper is the third in a series outlining the development of orally active sulfido peptide leukotriene antagonists containing a (quinolin-2-ylmethoxy)phenyl moiety. In this work the systematic variation of the acid side chain substituents led to dramatic and reproducible changes in the oral activity of these compounds, presumably due to alterations in their pharmacokinetic properties. The most potent compound identified, 5-[4-[4-(quinolin-2-yl-methoxy)phenyl]-3-methylbutyl]tetrazole (32), represents a convergence of good in vitro antagonist activity and a 3-10-fold improvement in oral potency over the current clinical candidate 2. The new findings from these optimization studies are as follows: oxygen substitution in the acid side chain was not necessary for antagonist activity, in vitro and in vivo activity was enhanced by alkyl or phenyl substitution on the gamma-carbon of the acid side chain of para-substituted (quinolin-2-ylmethoxy)phenyl derivatives, and free rotation about the side chain carbon atom adjacent to the (quinolin-2-ylmethoxy)phenyl ring was required for activity. The lead compound of this report (32) is a competitive inhibitor of [3H]LTD4 binding to receptor membrane purified from guinea pig lung (Ki = 12 +/- 3 nM) and of the spasmogenic activity of LTC4, LTD4, and LTE4 in guinea pig lung strip. Dosed orally in guinea pigs, this compound blocks LTD4-induced bronchoconstriction (ED50 0.8 mg/kg) and antigen-induced systemic anaphylaxis (ED50 = 1.2 mg/kg).

Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 1. Initial structure-activity relationships

This series of reports describes the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. Described in this first report are the structure-activity relationships that led to a more than a 20-fold improvement of the potency and selectivity of the initial chemical lead (RG 5901). From this series of compounds, RG 7152 (16) was identified and selected for further evaluation in the clinic as an antiasthmatic agent. Compound 16 competitively inhibits [3H]LTD4 binding to membranes from guinea pig lung (Ki = 38 +/- 6 nM) and the spasmogenic activity of LTC4, LTD4, and LTE4 in parenchymal lung strips from guinea pigs. Unlike the original lead (RG 5901), compound 16 does not inhibit 5-lipoxygenase from guinea pig PMNs. Following oral administration to guinea pigs, 16 blocks LTD4-induced dermal permeability (ED50 = 6.9 mg/kg), LTD4-induced bronchoconstriction (ED50 = 1.1 mg/kg), antigen-induced bronchoconstriction (ED50 = 2.5 mg/kg), and anaphylactic-induced mortality (ED50 = 16 mg/kg). These studies on structure-activity relationships indicate that there is a requirement for an acidic function and the presence of the (2-quinolinylmethoxy)phenyl moiety in a specific geometric arrangement.

Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene D4 receptor antagonists. 2. Effects of an additional phenyl ring on receptor affinity

This series of reports describe the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. The compounds reported in this paper contain an additional phenyl ring, which has significantly improved the receptor affinity. The effect of changes in the linkage between the two phenyl rings as well as the orientation of the acidic functional group on biological activity are discussed. Many of these compounds have high affinity to the sulfidopeptide leukotriene D4 receptors with Ki values ranging between 2 and 20 nM and are orally active. Compound 27 [RG 12525, 5-[[2-[[4-(2-quinolinylmethoxy)phenoxy]- methyl]phenyl]methyl]-1H-tetrazole] represents the best combination of in vitro and in vivo biological activity in this series and has been selected for further evaluation in clinical studies of asthma.

13C and 1H NMR studies of some aminoarsonium chlorides

Abstract13C and 1H NMR spectral data for a homologous series of tertiary arsines (R3As, where R = Me, Et, n‐Pr and Ph), aminoarsines and arsonium and aminoarsonium salts are reported and discussed. In nearly all cases, quaternization of the tertiary arsine to its corresponding arsonium or aminoarsonium salt causes a decrease in the magnitude of δc. These results are compared with those from an analogous study on the quaternization of tertiary phosphines, R3P. A discussion of the factors that affect the relative magnitudes of δc and R3As and R3P is given. Hammett‐Taft dual substituent parameter analysis was used to show that the positive charge on the arsenic in the atomatic quaternary salts is delocalized by an inductive mechanism. The 1H NMR spectra of the n‐propyl‐ and phenyl‐containing compounds are non‐first order. The δH and nJ(HH) values were determined by iterative computer analysis. Likewise, the nJ(CH) values for the phenyl carbons of [Ph3AsNH2]Cl and [Ph3AsNHMe]Cl were determined from the coupled 13C NMR spectra.