Identification and Quantification of the Main Psychoactive Ingredients of Cannabis in Urine Using Excitation-Eemission Matrix Fluorescence Coupled with Parallel Factor Analysis.

Cannabis is the most prevalent abused substance after alcohol, and its consumption severely harms human health and thus adversely impacts society. The identification and quantification of cannabis in urine play important roles in practical forensics. Excitation-emission matrix (EEM) fluorescence spectroscopy coupled with parallel factor (PARAFAC) analysis was developed to identify and quantify the four main ingredients of cannabis in urine samples. The main ingredients of cannabis including Δ-9-tetrahydrocannabinol (THC), cannabidiol, cannabinol, and tetrahydrocannabinolic acid (THC-COOH) exhibited diverse fluorescence characteristics, and the concentrations of these compounds depicted a positive linear relationship with the fluorescence intensity at the ng/mL level. The EEM/PARAFAC method adequately characterized and discriminated the four ingredients in calibration and prediction samples with a low root-mean-square error of prediction (RMSEP; 0.03-0.07 µg/mL) and limit of quantitation (LOQ; 0.26-0.71 µg/mL). The prediction results of the EEM/PARAFAC method well correlated with that of GC-MS with a low RMSEP range (0.01-0.05 µg/mL) and LOQ range (0.07-0.44 µg/mL) in urine samples. The EEM spectroscopic investigation coupled with the PARAFAC algorithm results in an organic, solvent-less, fast, reliable tool to perform accurate and rapid screening of cannabis abusers.

Identification and classification of ATS in oral fluid based on Ag nanoassemblies on Si surface doped with Au nanobipyramids.

Herein, a novel Ag NP substrate doped with Au nanobipyramids was designed and fabricated via a convenient procedure of galvanic reaction for the identification and classification of amphetamine-type stimulants (ATS) in oral fluids in combination with surface enhanced Raman scattering (SERS). The substrate was shown to have a three-dimensional nanostructure, high SERS activity, and good stability. In combination with SERS, the Ag NP substrate doped with Au nanobipyramids was able to detect ultra-low traces of ATS, including amphetamine, methylamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethylamphetamine (MDMA) in oral fluid with limit of detection (LOD) and limit of determination quantitation (LOQ) as low as 10-9 mg/mL, which is much better than the current spectroscopic techniques. The equations between concentration and peaks intensity for quantitative analysis displied good doublelogarithmic linear relations and reliability figures of merit at nanogram concentration level in compartion with GC-MS method. The approach can be broadly applied to the ultra-low trace detection of ATS in oral fluid and would be particularly useful for the analyses of nitrogenous organic compounds.

Molecular spectroscopic studies examining the interactions between phenobarbital and human serum albumin in alcohol consumption.

BACKGROUND: Alcohol dependence is associated with a wide range of serious mental, physical, and social consequences and is one of the most common chronic diseases worldwide. Barbiturates, which are a first-line treatment in the clinic for alcohol withdrawal, may result in combined barbiturate and alcohol use. Their co-use abuse may promote synergistic effects between barbiturates and alcohol in vivo. OBJECTIVE: To investigate the effects of different alcohol concentrations on the synergistic effects of phenobarbital and alcohol. METHODS: The interactions between phenobarbital and human serum albumin (HSA) and the effects of different alcohol concentrations on the binding behaviors of the phenobarbital-HSA system were investigated by molecular docking and spectroscopic methods, including fluorescence spectroscopy and UV-visible absorption spectroscopy. RESULTS: Experimental results revealed that phenobarbital can be stored and carried by HSA. The presence of alcohol (≤1.96 × 10-2 M) can increase the proportion of free phenobarbital and shorten the half-life and storage time of phenobarbital in the blood, thereby enhancing its bioactive efficacy. The binding constants (Kb) of the phenobarbital-HSA system decrease in the presence of alcohol (≥2.61 × 10-2 M), which suggests that phenobarbital should be quickly cleared from blood, thereby decreasing the activity of phenobarbital. CONCLUSIONS: The effects of alcohol on the transposition of phenobarbital by HSA at the beginning of the barbiturate metabolic process play an important role in the synergistic effects of phenobarbital and alcohol. This mechanism may be significant for the clinical dosage of patients with alcohol dependence.

Discovery of potential antifungal triazoles: design, synthesis, biological evaluation, and preliminary antifungal mechanism exploration.

A series of triazoles as miconazole analogues was designed, synthesized and characterized by IR, NMR, MS and HRMS. All the newly prepared compounds were screened for their antifungal activities against five kinds of fungi. The bioactive assay showed that most of the synthesized compounds exhibited good or even stronger antifungal activities in comparison with the reference drugs miconazole and fluconazole. In particular, the 3,4-dichlorobenzyl derivative 5b showed a comparable or superior activity against all the tested fungal strains to standard drugs, and formed a supramolecular complex with CYP51 via the hydrogen bond between the 4-nitrogen of the triazole nucleus and the histidine residue. Preliminary experiments revealed that both of the active molecules 5b and 9c could intercalate into calf thymus DNAs, which might block DNA replication to exhibit their powerful antifungal abilities. Further studies indicated that compound 5b might be stored and transported by human serum albumin through hydrophobic interactions, specific electrostatic interactions and hydrogen bonds. These results strongly suggested that compound 5b could serve as a promising antifungal candidate.

Novel 3-Aminothiazolquinolones: Design, Synthesis, Bioactive Evaluation, SARs, and Preliminary Antibacterial Mechanism.

A series of novel 3-aminothiazolquinolones as analogues of quinolone antibacterial agents were designed and synthesized in an effort to circumvent quinolone resistance. Among these 3-aminothiazolquinolones, 3-(2-aminothiazol-4-yl)-7-chloro-6-(pyrrolidin-1-yl) quinolone 12b exhibited potent antibacterial activity, low cytotoxicity to hepatocyte cells, strong inhibitory potency to DNA gyrase, and a broad antimicrobial spectrum including against multidrug-resistant strains. This active molecule 12b also induced bacterial resistance more slowly than norfloxacin. Analysis of structure-activity relationships (SARs) disclosed that the 2-aminothiazole fragment at the 3-position of quinolone plays an important role in exerting antibacterial activity. Molecular modeling and experimental investigation of aminothiazolquinolone 12b with DNA from a sensitive methicillin-resistant Staphylococcus aureus (MRSA) strain revealed that the possible antibacterial mechanism might be related to the formation of a compound 12b-Cu(2+)-DNA ternary complex in which the Cu(2+) ion acts as a bridge between the backbone of 3-aminothiazolquinolone and the phosphate group of the nucleic acid.

Novel hybrids of metronidazole and quinolones: synthesis, bioactive evaluation, cytotoxicity, preliminary antimicrobial mechanism and effect of metal ions on their transportation by human serum albumin.

A novel series of hybrids of metronidazole and quinolones as antimicrobial agents were designed and synthesized. Most prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. Furthermore, these highly active metronidazole-quinolone hybrids showed appropriate ranges of pKa, log P and aqueous solubility to pharmacokinetic behaviors and no obvious toxicity to A549 and human hepatocyte LO2 cells. Their competitive interactions with metal ions to HSA revealed that the participation of Mg(2+) ion in compound 7d-HSA association could result in a concentration increase of free compound 7d. Molecular modeling and experimental investigation of compound 7d with DNA suggested that possible antibacterial mechanism might be in relation with multiple binding sites between bioactive molecules and topo IV-DNA complex.

Synthesis and bioactive evaluation of a novel series of coumarinazoles.

A series of novel coumarinazoles were designed, synthesized, and characterized by IR, NMR, MS and HRMS spectra. The bioactive assay for the newly prepared compounds against six bacteria and five fungi manifested that most new compounds exhibited good or even stronger antibacterial and antifungal activities in comparison with reference drugs Chloromycin, Norfloxacin and Fluconazole. Bis-azole alcohols 7a and 7d-e showed better anti-Candida utilis activity than mono-azole derivatives 4a and 4d-e at the tested concentrations, and they were more potent than the clinical Fluconazole. While triazole alcohol 7a gave comparable anti-Candida albicans and anti-Candida mycoderma activity to Fluconazole and better anti-MRSA activity than mono-triazole one 4a and clinical Norfloxacin. 1H-Benzoimidazol-2-ylthio coumarin derivatives 4e and 7e gave the strongest anti-Escherichia coli JM109 efficacy. Oxiran-2-ylmethoxy moiety was found to be a beneficial fragment to improve antibacterial and antifungal activity to some extent.

Synthesis and biological evaluation of a class of quinolone triazoles as potential antimicrobial agents and their interactions with calf thymus DNA.

A novel series of quinolone triazoles were synthesized and characterized by IR, NMR, MS and HRMS spectra. All the newly prepared compounds were screened for their antimicrobial activities against seven bacteria and four fungi. Bioactive assay manifested that most of new compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains including multi-drug resistant MRSA in comparison with reference drugs Norfloxacin, Chloromycin and Fluconazole. The preliminary interactive investigations of compound 6b with calf thymus DNA by fluorescence and UV-vis spectroscopic methods revealed that compound 6b could effectively intercalate DNA to form compound 6b-DNA complex which might block DNA replication and thus exert its antimicrobial activities.

catena-Poly[[trans-bis-(cyclo-hexane-1,2-diamine-κ²N,N)cadmium]-µ-iodido-(diiodidocadmium)-µ-iodido].

In the title compound, [Cd2I4(C6H14N2)2](n), there are two independent Cd(II) ions. One Cd(II) ion is coordinated in a slightly distorted octa-hedral coordination environment by four N atoms from two cyclo-hexane-1,2-diamine ligands and two iodido ligands. The other Cd(II) ion is coordinated by four iodido ligands in a slightly distorted tetra-hedral coordination environment. Two of the iodido ligands act as bridging ligands connecting Cd(II) ions and forming a one-dimensional polymer along [010]. In the crystal, N-H⋯I hydrogen bonds connect the one-dimensional structure into a two-dimensional framework parallel to (001).

(Z)-1,3-Bis(4-chloro-phen-yl)-2-(1H-1,2,4-triazol-1-yl)prop-2-en-1-one.

In the title mol-ecule, C(17)H(11)Cl(2)N(3)O, the C=C bond connecting the triazole and 4-chloro-phenyl groups adopts a Z geometry. The dihedral angles formed by the triazole ring and the 4-chloro substituted benzene rings are 67.3 (1) and 59.1 (1)°. The dihedral angle between the two benzene rings is 73.5 (1)°.