Spectroscopic Trends for the Determination of Illicit Drugs in Oral Fluid

Abstract

The present work aims to review all of the articles published so far, focused on the determination of drugs of abuse in oral fluid. This fluid provides a simpler, faster, and more controllable sampling in comparison with the other biological fluids, such as blood or urine. Actually, the main goal of the researchers is to lower the limit of detection (LOD) to detect quantities of drugs smaller than the cut-off limits established by law for drug controls. Advances in Raman, infrared (IR), and nuclear magnetic resonance (NMR) spectroscopy applications are discussed. Surface-enhanced Raman spectroscopy (SERS) has been shown as the most sensitive technique for the detection of illicit drugs in oral fluid. The use of IR spectroscopy for determining drugs of abuse in oral fluid is growing, although the LODs obtained until now do not yet satisfy the necessities in the forensic field. Finally, NMR spectroscopy has seldom been used to determine drugs in oral fluid. Another future trend seems to be related with the use of portable instrumentation, which would allow us to perform in-situ analysis. This last application seems to be particularly promising to perform roadside drug tests and to identify overdose drugs in patients in emergency conditions.     

An Overview of 195Pt Nuclear Magnetic Resonance Spectroscopy

Abstract

This brief, non‐exhaustive review describes some basic theoretical aspects of ¹⁹⁵Pt nuclear magnetic resonance spectroscopy and also the empirical approach used by the researchers in the field. The different factors which influence the chemical shifts are discussed. The couplings constants between ¹⁹⁵Pt and other isotopes, which have a spin of 1/2 (such as, ¹H and ¹³C) bring further important information on the structures of Pt compounds. Recently, ¹⁹⁵Pt‐NMR spectroscopy in the liquid state has been used successfully in many research fields, e.g., the determination of enantiomeric composition and absolute configuration, in the area of biosensors and biomarkers, in cluster chemistry, in cancer research and in kinetic studies. While liquid‐state ¹⁹⁵Pt‐NMR spectroscopy encompasses a wide range of areas, the parallel solid‐state technique has only been employed over the past few years, mainly in studies of heterogeneous catalysis and is more industrially oriented.     

Azetidin‐2‐one Versus Chroman‐2‐one: Application of 1H‐13C COSY NMR and Mass Spectroscopy in Structure Elucidation–Class of Compounds

Azetidin‐2‐ones, commonly known as β‐lactams, constitute a biologically important class of compound. Treatment of azetidin‐2‐ones with alkali is known to form diverse types of compounds depending on the stability of the ring. In many cases, the ring is retained in the product at the cost of transformation of substituents. Spectroscopy is the most important tool to characterize the organic compounds. However, in some cases the structures of the products are so closely related that simple IR, ¹H NMR, and ¹³C NMR spectra do not lead to unambiguous structure elucidation. This article reports a novel application of ¹H‐¹³C COSY NMR and mass spectroscopy in determining unequivocally an azetidin‐2‐one ring structure instead of a chroman‐2‐one ring structure for the product obtained by treatment of 1‐benzhydryl‐3,3‐bis(4‐methylphenyl)‐4‐[2‐(o‐dip‐tolylacyl)hydroxyphenyl]‐2‐azetidinone with ethanolic sodium hydroxide at room temperature.     

Recent advances in linear and non‐linear Raman spectroscopy. Part IX

This annual review is published to provide an overview of advances in the field of Raman spectroscopy as reflected in papers published each year in the Journal of Raman Spectroscopy (JRS) as well as in trends across related journals that have published papers in the broad field of Raman spectroscopy. The content is obtained from statistical data on article counts obtained from Thomson Reuters ISI Web of Science Core Collection by year and by subfield of Raman spectroscopy. Additional information is gleaned from presentations at the VIII International Conference on Advanced Vibrational Spectroscopy (ICAVS‐8) in Vienna, Austria in July 2015 and those featuring Raman scattering at SCIX 2015 organized by the Federation of Analytical Chemistry and Spectroscopy Societies (FACSS) in Providence, Rhode Island, USA, in September/October 2015. Coverage is also provided for topics from the conference ECONOS 2015 held in April in Leuven, Belgium. Finally, papers published in JRS in 2014 are highlighted and arranged by topics at the frontier of Raman spectroscopy. Taken from these various viewpoints, it is clear that Raman spectroscopy continues to be a rapidly expanding field that provides sensitive photonic information of matter at the molecular level in an ever‐widening arena of novel applications. Copyright © 2015 John Wiley & Sons, Ltd.     

Stereochemical Elucidation of Norbornene Derivatives Synthesized as Leukotriene D4 Receptor Antagonists

The complete ¹H and ¹³C NMR assignment and stereochemical elucidation of four norbornene derivatives (1–4) are presented. These derivatives were obtained by an asymmetric Diels–Alder reaction of a chiral dienophile, from D‐glucose, as leukotriene D4 receptor antagonists. NOE measurements of the four products between H‐7b and H‐5 readily allowed discrimination between exo‐ (2, 4) and endo‐ (1, 3) diastereomers with respect to methyl carboxylate and tetrahydrofuro[1,3]dioxolyl groups. Further discrimination and subsequent absolute configuration determination of the two endo‐ and two exo‐ products were performed by NOE peak measurements and molecular modeling calculations of relative interproton distances of the most stable conformations of each isomer.     

Review of Chemometrics Applied to Spectroscopy: 1985-95, Part 3 — Multi-way Analysis

INTRODUCTION

In this third part of a review on chemometrics in spectroscopy we will describe a recent methodology that has attracted increasing interest in spectroscopy. namely multi-way analysis. The application of multi-way analysis in spectroscopy is still relatively new. hence many methodological improvements are being investigated currently. Part of thls review will also be used to describe the algorithmic improvements gained the last decade.     

A Review of Applications and Experimental Improvements Related to Diode Laser Atomic Spectroscopy

Abstract

This article attempts to review the major advancements made in the past 12 years, since 1993, in the field of diode laser atomic spectroscopy. The discussion covers experimental improvements (e.g., wavelength stabilization, frequency upconversion, enhancement of tuning characteristics, spectral bandwidth using external cavities, etc.), diagnostic applications in various atomizers, as well as analytical applications (e.g., absorption, fluorescence, and ionization spectroscopy; element‐selective detectors for chromatography; etc.). With potential new users of these methods in mind, a detailed overview of the properties relevant to atomic spectroscopy of commercial diode lasers is also given.     

NMR Studies of Hindered Rotation and Magnetic Anisotropy: The Diels–Alder Adducts of Phencyclone with N‐Phenylmaleimide and N‐(2‐Trifluoromethylphenyl)maleimide. Ab Initio Calculations for Optimized Structures

Abstract

N‐Phenylmaleimide, 2, and N‐(2‐trifluoromethylphenyl)maleimide, 3, were separately added to phencyclone, 1, to yield the corresponding phencyclone Diels–Alder adducts, 4 and 5. The resulting adducts (and some precursors) have been characterized by one‐ and two‐dimensional ¹H and ¹³C NMR at 300 and 75 MHz, and by ¹⁹F NMR at 282 MHz, at ambient temperatures. The NMR data are consistent, for both adducts, with: (a) hindered rotation of the bridgehead unsubstituted phenyl groups about the C(sp²)–C(sp³) bonds, based on slow exchange limit (SEL) spectra and (b) endo adduct configuration based on magnetic anisotropic effects in the ¹H NMR. The NMR spectra of the phencyclone adduct, 4, of N‐phenylmaleimide, indicate free rotation on the NMR timescales (fast exchange limit, FEL spectra) about the N‐phenyl bond. The spectra for the adduct, 5, of N‐(2‐trifluoromethylphenyl)maleimide are interpreted as consistent with SEL regimes, for the N‐aryl rotations, with a single rotamer present in which the trifluoromethyl group is directed “out of” the adduct cavity, and away from the phenanthrenoid moiety. This conclusion is based, in part, on NMR data suggesting the apparent slow N‐aryl bond rotation in a pair of atropisomers corresponding to the acetic acid addition products from the N‐(2‐trifluoromethylphenyl)maleimide. Evidence of magnetic anisotropic effects due to the phenanthrenoid moiety and proximal carbonyls is discussed. ¹H, ¹³C, and ¹⁹F assignments are presented and interpreted. Molecular modeling calculations at the Hartree–Fock level, 6‐31G* basis set, were performed to provide geometry optimizations for energy‐minimized structures of selected compounds.     

13C Nuclear Magnetic Resonance Studies of the Conformations of Serine‐3′‐ and 5′‐Thymidine Monophosphate Conjugates

The differences in the backbone conformation between O‐thymidine‐3′‐(1) and 5′‐yl O‐alkyl N‐phosphoryl serine methyl esters (2) have been investigated by solution ¹³C NMR spectroscopy. The stereo‐sensitive vicinal ³¹P–¹³C coupling constants were measured and used in the conformational analysis for the P–O5′–C5′, P–O3′–C3′, and P–N–C_α bonds. Three‐dimensional structural characteristics of dephosphorylation reactions of Compounds are also discussed.     

Nuclear magnetic resonance of 55Mn in the antiferromagnet CsMnBr3 in a variable longitudinal magnetic field

The spectrum and intensities of NMR lines are investigated experimentally and theoretically for excitation by an alternating magnetic field h‖ parallel to a static field H in the quasi-one-dimensional, six-sublattice antiferromagnet CsMnBr₃. According to theory, two new NMR lines, which are not excited by a transverse magnetic field h _⊥, are observed near the phase transition from triangular to collinear structure (H=H _c ) [JETP 86, 197 (1998)]. Zh. éksp. Teor. Fiz. 115, 2228–2241 (June 1999)     

Proton and Carbon‐13 NMR Studies of Some Tryptamines,Precursors, and Derivatives: Ab Initio Calculations for Optimized Structures

Abstract

Proton and carbon‐13 NMR data are presented for 5‐methoxytryptamine, 1; 6‐methoxytryptamine, 2; N,N‐diisopropyl‐5‐methoxytryptamine, 3, (5‐MeO‐DIPT); and N,N‐diisopropyl‐5‐methoxyindole‐3‐glyoxylamide, 4, at 300 MHz (¹H) and 75 MHz (¹³C) in CDCl₃ at ambient temperature. Compound 3, considered a potential hallucinogen, had been placed into Schedule I of the Controlled Substances Act, effective April 4, 2003, by the U.S. Drug Enforcement Administration. Compound 4 can serve as a possible precursor to 3. We believe that these are the first proton NMR assignments obtained at medium field (7 tesla) using selective homodecoupling and two‐dimensional homonuclear chemical shift correlation spectra (using one or more of the COSY45, COSY90, and COSYLR experiments) for rigorous aryl proton assignments in this group of compounds. Significant observed differences in the proton and carbon‐13 NMR spectra should allow facile distinction of the 5‐methoxy series, 1 and 3, from the 6‐methoxy series, 2. Energy minimizations to obtain optimized structures for each compound were performed at the Hartree–Fock level with the 6‐31G* basis set, and the resulting geometries are discussed. The presented geometry calculations appear to be the most accurate reported to date for 1 based on the basis set employed, and the first HF/6‐31G* structures for compounds 2, 3, or 4. Appreciable geometry differences in 3 and 4 for the pendant sidechain containing the N[CH(CH₃)₂]₂ moiety are noteworthy. Proximity of the carbonyl oxygens in 4 to H2 and H4 is suggested as a possible contributing factor in the deshielding of these protons in the NMR spectrum.     

Recent Analytical Applications of Molecular Spectroscopy in Bioorganometallic Chemistry—Part I: Metal Carbonyls

Abstract: This is the first part of a two-part review on the analytical applications of molecular spectroscopy in bioorganometallic chemistry since 2005. In this case, radiopharmaceutical studies are included and the review is focused particularly on biological molecules labeled with metal carbonyl fragments.     

Investigation of damaged interior walls using synchrotron‐based XPS and XANES

Evidence of internal sulfate attack in field exposure was demonstrated by the damaged interior wall of a three‐year‐old house situated in Nakhon Ratchasima Province, Thailand. Partial distension of the mortar was clearly observed together with an expansion of a black substance. Removal of the black substance revealed a dense black layer. This layer was only found in the vicinity of the damaged area, suggesting that this black material is possibly involved in the wall cracking. By employing synchrotron‐based X‐ray photoelectron spectroscopy (XPS) and X‐ray absorption near‐edge structure (XANES) techniques, the unknown sample was chemically identified. The S 2p and O 1s XPS results mutually indicated the existence of sulfate species in the materials collected from the damaged area. The XANES results indicated the presence of ferrous (II) sulfate, confirming sulfate‐induced expansion and cracking. The sulfate attack in the present case appeared to physically affect the structure whereas the chemical integrity at the molecular level of the calcium silicate hydrate phase was retained since there was a lack of spectroscopic evidence for calcium sulfate. It was speculated that internal sulfate probably originated from the contaminated aggregates used during the construction. The current findings would be beneficial for understanding the sulfate‐attack mechanism as well as for future prevention against sulfate attack during construction.     

Structural Assignment of Stilbenethiols and Chalconethiols and Differentiation of Their Isomeric Derivatives by Means of 1H‐ and 13C‐NMR Spectroscopy

Abstract

The ¹H‐ and ¹³C‐NMR spectra of some substituted stilbenes and chalcones were assigned unambiguously on the basis of a combination of homo‐ (COSY) and heteronuclear (HETCOR) two‐dimensional methods, the chemical shifts, as well as spin‐coupling constants. The A_ik empirical parameters of the –O–C(S)–N(CH₃)₂, –S–C(O)–N(CH₃)₂, and –SH group were calculated to help predict the chemical shifts of substituted stilbenes, 4′‐nitrostilbenes, and chalcones. The ¹H‐ and ¹³C‐NMR spectra have been shown to be able to differentiate between the isomers of O‐stilbenyl (4, 5) and S‐stilbenyl N,N‐dimethylthiocarbamates (7, 8) as well as O‐chalconyl (6) and S‐chalconyl N,N‐dimethylthiocarbamates (9).     

Nuclear Magnetic Resonance Spectroscopy Study of a Disaccharidic Crown Ether.

Abstract

The disaccharidic anhydro derivative 6-O-(5,6-anhydro-3-deoxy-1,2-O-isopropylidene α-D-glucofuranos-3-yl)-1,2-O-isopropylidene-3-O-n-dodecyl-α-D-glucofuranose (1) led to the disaccharidic crown ether 2 in 40% yield when treated at low concentration with 2.5 eq. of KOH in toluene-Me₂SO. Compound 2 structure was proved through a detailed NMR analysis (¹H, ¹³C, ¹H-¹H and ¹³C-¹H 2D correlations). This structural elucidation indicated that compound 2 resulted from the intramolecular attack of the C-5-O^?alkoxide group, generated in the basic medium, on the C-6′ carbon of the 5′,6′-anhydro group.     

NMR Studies of Crowded Diels–Alder Adducts of Phencyclone with N‐(2,6‐Dialkylphenyl)maleimides. Hindered Rotations and Magnetic Anisotropy

Abstract

Phencyclone, 1, reacted with N‐(2,6‐dimethylphenyl)maleimide, 2a; with N‐(2,6‐diethylphenyl)maleimide, 2b; and with N‐(2,6‐diisopropylphenyl)maleimide, 2c, respectively, to yield the corresponding Diels–Alder adducts, 3a–c. The adducts were extensively characterized by NMR (7 T) at ambient temperatures using one‐ and two‐dimensional (1D and 2D) proton and carbon‐13 techniques for assignments. Slow exchange limit (SEL) spectra were observed, demonstrating slow rotations on the NMR timescales, for the unsubstituted bridgehead phenyl groups [C(sp³)–C(aryl sp²) bond rotations] and for the 2,6‐dialkylphenyl groups [N(sp²)–C(aryl sp²) bond rotations]. Substantial magnetic anisotropic shifts were seen in the adducts. For example, in the N‐(2,6‐dialkylphenyl) moieties of the adducts, one of the alkyl groups is directed “into” the adduct cavity, toward the phenanthrenoid portion, and these “inner” alkyl proton NMR signals were shifted upfield. Thus, in CDCl₃, the “inner” methyl of adduct 3a exhibits a proton resonance at ?0.13 ppm, upfield of tetramethylsilane (TMS); the “inner” ethyl group signals from 3b appear at 0.026 ppm (CH₂, quartet), and ?0.21 ppm (CH₃, triplet); and the “inner” isopropyl group from 3c is seen at ?0.06 ppm (methine, approx. septet) and ?0.39 ppm (CH₃, doublet). Proton NMR of the crude N‐(2,6‐dialkylphenyl)maleamic acids (used as precursors of the maleimides, 2a–c) exhibited two sets of AB quartet signals, suggesting possible conformers from hindered rotation in the amide groups about the HN–C?O bonds.     

Development and exploration of a new methodology for the fitting and analysis of XAS data

A new data analysis methodology for X‐ray absorption near‐edge spectroscopy (XANES) is introduced and tested using several examples. The methodology has been implemented within the context of a new Matlab‐based program discussed in a companion related article [Delgado‐Jaime et al. (2010), J. Synchrotron Rad. 17 , 132–137]. The approach makes use of a Monte Carlo search method to seek appropriate starting points for a fit model, allowing for the generation of a large number of independent fits with minimal user‐induced bias. The applicability of this methodology is tested using various data sets on the Cl K‐edge XAS data for tetragonal CuCl₄^2?, a common reference compound used for calibration and covalency estimation in M—Cl bonds. A new background model function that effectively blends together background profiles with spectral features is an important component of the discussed methodology. The development of a robust evaluation function to fit multiple‐edge data is discussed and the implications regarding standard approaches to data analysis are discussed and explored within these examples.     

Proton and Carbon‐13 NMR Studies of the Phencyclone Adducts of Medium Alkyl Chain‐Length N‐n‐Alkylmaleimides. Hindered Rotations and Magnetic Anisotropic Effects. Ab initio Calculations for Optimized Structures

Abstract

The Diels–Alder adducts, 3a–e, of phencyclone, 1, have been prepared from a series of N‐n‐alkylmaleimides, 2, with medium chain‐length n‐alkyl groups. The maleimides were obtained by cyclodehydration of the N‐n‐alkylmaleamic acids, 4, formed from reaction of maleic anhydride with the corresponding n‐alkylamines. The five adducts prepared included derivatives from n‐heptyl, 3a; n‐octyl, 3b; n‐nonyl, 3c; n‐decyl, 3d; and n‐dodecyl, 3e. The NMR spectra of the adducts were studied in CDCl₃ at ambient temperatures at 300 MHz for proton and 75 MHz for carbon‐13, with full proton assignments achieved by high‐resolution COSY45 spectra for the aryl and the alkyl regions. Slow exchange limit (SEL) spectra were observed for both ¹H and ¹³C spectra showing slow rotation on the NMR timescales of the unsubstituted bridgehead phenyl groups. Endo Diels–Alder adduct stereochemistry was supported by striking magnetic anisotropic shielding effects in the ¹H spectra of the alkyl groups, with the NCH₂ CH ₂ signal of each adduct appearing upfield of tetramethylsilane (TMS) at ca. ?0.32 ppm. Proton NMR spectra for precursor maleamic acids and maleimides are reported, with some solvent effects found (CDCl₃ vs. d ₆‐acetone) for the carbon‐bound HC?CH protons of 4. Ab initio molecular modeling calculations at the Hartree‐Fock level using the 6‐31G* basis set have been performed for two key conformers of the phencyclone adduct of N‐n‐octylmaleimide, as a representative structure for these hindered adducts, to estimate geometric parameters for the adduct. A syn conformer, with the alkyl chain directed into the adduct cavity, was found to be ca. 0.23 kcal/mol lower energy than an anti conformer (in which the alkyl chain was directed away from the phenanthrenoid moiety).     

NMR in 55Mn2+ nuclei in the quasi-one-dimensional antiferromagnetic CsMnBr3

The NMR spectrum of the quasi-one-dimensional easy-plane antiferromagnetic CsMnBr₃, which has trigonal spin lattice, is investigated in detail. The measurements were performed on a wide-band NMR decimeter microwave-band spectrometer over a wide range of magnetic fields at temperatures 1.3–4.2 K. All three branches of the NMR spectrum previously found by us [JETP Lett. 64, 225 (1996)] are severely distorted because of the dynamic interaction with the Goldstone mode in the antiferromagnetic resonance spectrum. The experimental results in fields up to 40 kOe are described satisfactorily by an equation obtained by Zaliznyak et al. [JETP Lett. 64, 473 (1996)]. Formulas are obtained in our work that agree very well with experiment at all fields up to the “collapse” field H _c of all sublattices. The unbiased NMR frequency in CsMnBr₃ is determined to be v _n0=416 MHz (T=1.3 K) in zero external magnetic field, and in this way the reduction in the spontaneous moment due to the quasi-one-dimensional nature of the system of Mn²⁺ spins, which according to our data amounts to 28%, is determined more accurately. The field dependences of the directions of the magnetic sublattices with respect to the magnetic field are obtained from the NMR spectra, confirming the equations of Chubukov [J. Phys. Condens. Matter 21, 441 (1988)]. The results on the field dependence of the width and intensities of the NMR lines are discussed, along with three observed anomalies: 1) a strong increase in the NMR frequency for nuclei in sublattices that are perpendicular to the magnetic field; 2) the nonmonotonic temperature dependence of the resonance field for the lower branch of the spectrum; 3) the presence of two branches of the NMR spectrum in large H _c fields, in which the CsMnBr₃ must be a quasi-one-dimensional antiferromagnetic. Zh. éksp. Teor. Fiz. 113, 352–368 (January 1998) Deceased.     

Characterization of Mango Juice by High‐Resolution NMR,Hyphenated NMR,and Diffusion‐Ordered Spectroscopy

Abstract

The application of nuclear magnetic resonance (NMR) spectroscopy, hyphenated NMR, and diffusion‐ordered spectroscopy (DOSY) to the characterization of mango juice, as an example of a complex food mixture, is described. The compositional changes taking place as a function of ripening were followed, and selected metabolites were quantified by integration of the corresponding NMR peaks. In this way, an overall view of the metabolite changes is obtained, enabling the study of the biochemical mechanisms involved in the ripening process. More than 50 compounds were identified by 1D‐ and 2D‐NMR, but many ambiguous assignments remain due to spectral overlap or insufficient coupling information. The use of Liquid Chromatography (LC‐NMR) and LC‐NMR/Mass Spectrometry (MS) enables a fuller characterization of the soluble pectin fraction to be made; its dependence on ripening stage is discussed. Finally, DOSY adds information on the M_r of many metabolites, including the pectin fractions of ripe and unripe mango juices, and enables further peak assignments to be made.