Extension of fourier transform vibrational circular dichroism into the near-infrared region: continuous spectral coverage from 800 to 10 000 cm(-1)

We report the first vibrational circular dichroism (VCD) spectra with continuous coverage from 800 cm(-1) in the mid-infrared (MIR) region to 10 000 cm(-1) in the near-infrared (NIR) region. This coverage is illustrated with MIR and NIR absorbance and VCD spectra of 2,2-dimethyl-dioxolane-4-methanol (DDM), alpha-pinene, and camphor that serve as calibration samples over this entire region. Commercially available, dual-source Fourier transform (FT) MIR and NIR VCD spectrometers were equipped with appropriate light sources, optics, and detectors, and were modified for dual-polarization-modulation (DPM) operation. The combination of liquid-nitrogen- and thermoelectric-cooled HgCdTe (MCT) detectors, as well as InGaAs and Germanium (Ge) detectors operating at room temperature, permitted collection of the desired absorbance and VCD spectra across the range of vibrational fundamental, combination band, and overtone frequencies. The spectra of DDM and alpha-pinene were measured as neat liquids and recorded for both enantiomers in the various spectral regions. Spectra for camphor were all measured in CCl(4) solution at a concentration of 0.6 M, except for the carbonyl-stretching region, where a more dilute concentration was used. The typical anisotropy ratios (g) of the three molecules were estimated with respect to their strongest VCD bands in each spectral region. It was found that for all three molecules in the spectral regions above 2000 cm(-1), anisotropy ratios are approximately the same order (10(-5)) of magnitude. However, in the MIR region, the typical anisotropy ratios are significantly different for the three molecules. This study demonstrates that with modern FT-VCD spectrometers modified for DPM operation, VCD spectra can be measured continuously across a wide spectral range from the MIR to nearly the visible region with an unsurpassed combination of signal-to-noise ratio and spectral resolution.     

Transmission fourier transform Raman spectroscopy of pharmaceutical tablet cores

Transmission Fourier transform (FT) Raman spectroscopy of pharmaceutical tablet cores is demonstrated using traditional, unmodified commercial instrumentation. The benefits of improved precision over backscattering Raman spectroscopy due to increased sample volume are demonstrated. Self-absorption effects on analyte band ratios and sample probe volume are apparent, however. A survey of near-infrared (NIR) absorption spectra in the FT-Raman spectral range (approximately 0 to 3500 wavenumber shift from 1064 nm, or 1064 to 1700 nm) of molecules with a wide range of NIR-active functional groups shows that although absorption at the laser wavelength (1064 nm) is relatively small, some regions of the Raman spectrum coincide with NIR absorbances of 0.5 per cm or greater. Fortunately, the pharmaceutically important regions of the Raman shift spectrum from 0 to 600 cm(-1) and from 1400 to 1900 cm(-1) exhibit low self-absorption for most organic materials. A statistical analysis of transmission FT-Raman noise in spectra collected from different regions of a pharmaceutical tablet provides insight into both spectral distortion and reduced sampling volume caused by self-absorption.     

Enantiomeric excess determination by fourier transform near-infrared vibrational circular dichroism spectroscopy: simulation of real-time process monitoring

The first use of near-infrared (NIR) Fourier transform vibrational circular dichroism (FT-VCD) to follow changes in the enantiomeric excess (EE) of chiral sample molecules in time using a flow-cell sampling apparatus is reported. Simultaneous changes in the fractional composition and the EE of a mixture of two different chiral molecules were monitored as a function of time. This simulates the progress of the chemical reaction from a chiral reactant to a chiral product where the mole fractions and EE values of both species may change with time. For the molecules studied, alpha-pinene, camphor, and borneol, the accuracy of following EE changes for one species alone is approximately 2%, while for simultaneously following EE changes in two species it is approximately 3% for 30 min sampling periods at 16 cm(-1) spectral resolution. These findings demonstrate the potential for VCD to be used in the NIR region for real-time monitoring of the composition and %EE of chemical reactions involving the synthesis of chiral molecules.     

Infrared intracavity laser absorption spectroscopy with a continuous-scan Fourier-transform interferometer

High-quality broadband infrared high-resolution spectra were obtained by use of the intracavity laser absorption spectroscopy technique with a Ti:sapphire laser in combination with a continuous-scan Fourier-transform (FT) interferometer. With electronic filtering used to smooth out the fluctuations of the laser power, the absorption of atmospheric water vapor in the range of 12,450-12,700 cm(-1) was recorded at a resolution of 0.05 cm(-1). A signal-to-noise ratio of greater than 300 was observed in this spectrum, corresponding to a minimum detectable absorption of approximately 2 x 10(-9) cm(-1). Comparison with previous measurements by use of a conventional FT technique shows that this method gives absorption spectra with highly accurate line positions along with reasonable line intensities. Investigation of the evolution of intracavity laser absorption spectra with the generation time is also shown to be possible with a continuous-scan FT spectrometer by use of the interleave rapid-scan method.     

Regional difference of water content in human skin studied by diffuse-reflectance near-infrared spectroscopy: consideration of measurement depth

Diffuse reflectance (DF) spectra in the 1250-2500 nm region were measured in vivo for the skin of the forehead, cheek, jaw, elbow, volar forearm, palm, knee, and heel of seven healthy volunteers, using a Fourier transform near-infrared (FT-NIR) spectrophotometer with a fiber-optic probe. Apparent regional differences of water content in the skin, as estimated from the diffuse reflectance NIR spectra, are discussed in relation to the influence of measurement depth. The NIR spectra were collected with or without a 300 microm gap between the fiber-optic probe and the skin surface. For comparison, in vitro NIR spectra of stratum corneum sheets equilibrated at 41, 50, 63, and 81% relative humidity, at 25 degrees C, were also obtained. There was a difference in the ratio of the two water bands centered near 1450 nm and 1900 nm between the contact and non-contact measurements. In addition, regional differences of water content calculated from the peak height of the 1900 nm water band, which was normalized to the peak height of the 2175 nm amide band, were compared. The results of Monte Carlo simulation indicated that the apparent regional differences arise at least in part from differences in the measurement depth due to differences in specular reflection at the skin surface and in the thickness of the stratum corneum.     

Near-infrared characterization on the secondary structure of regenerated Bombyx mori silk fibroin

Several advantages of the near-infrared (NIR) technique in the characterization of the secondary structure of regenerated Bombyx mori silk fibroin are demonstrated. Silk fibroin films with thicknesses ranging from 50 to 300 microm are suitable for the NIR measurement. The bands due to hydrogen-bonded water are independent in the NIR spectra and facilitate our investigation of the amide region. Analysis of the combination modes of amide groups in the NIR spectra could lead to a profile of conformation ratio of silk fibroin, which was supported by nuclear magnetic resonance (NMR) observations.     

Short-wave near-infrared spectroscopy of biological fluids. 1. Quantitative analysis of fat, protein, and lactose in raw milk by partial least-squares regression and band assignment

The present study has aimed at providing new insight into short-wave near-infrared (NIR) spectroscopy of biological fluids. To do that, we analyzed NIR spectra in the 800-1,100-nm region of 100 raw milk samples. The contents of fat, proteins, and lactose were predicted by partial least-squares (PLS) regression and band assignment in that region was investigated based upon PLS loading plots and regression coefficients. For the fat prediction, the whole set of samples was divided into two groups and the fat concentration was predicted for the samples that were not included in the calibration procedures. The correlation coefficient and root-mean-square error of prediction (RM-SEP) in the better prediction run were found to be 0.996 and 0.087 wt %, respectively. Assignment of the bands due to fat was proposed based upon the regression coefficients and PLS loading weights, and the importance of a pretreatment in the prediction was discussed. Milk proteins also yielded sufficient correlation coefficients and RMSEP although the contributions of protein bands to the milk spectra were much smaller than those of the fat bands. The sizes of the calibration models for protein prediction were considered. This is the first time that good correlation coefficients and RMSEP of proteins have ever been obtained for the short-wave NIR spectra of milk. For lactose, noisy regression coefficients with limited prediction ability were obtained. Band assignment was investigated also for bands due to proteins and lactose. We propose the detailed band assignment for the short-wave NIR region useful for various biological fluids. The results presented here demonstrate that the short-wave NIR region is promising for the fast and reliable determination of major components in biological and biomedical fluids.     

Theoretical simulation of a polarization modulator based on mechanical rotation of a polarizing element

The properties of three alternative designs for a polarization modulator of potential use for the measurement of vibrational circular dichroism (VCD) are evaluated and compared by use of Mueller calculus. The analysis shows that the combination of a fixed polarizer plus either a photoelastic modulator or a rotating quarter-wave plate possesses nearly the same capability for generation of time-varying, circularly polarized light. However, a modulator composed of a rotating polarizer plus a fixed birefringent plate entails considerable theoretical and experimental difficulties for use in the measurement of VCD spectra. While VCD spectra obtained with the rotating devices can be calibrated in the same manner as spectra obtained with a photoelastic modulator, Mueller analysis shows that the form of the resultant calibration signal will have a different shape. The relevant expressions for VCD and linear dichroism as well as the calibration signals are presented, and consequences for practical realization of these experiments are discussed.     

Vibrational circular dichroism of matrix-assisted amino acid films in the mid-infrared region

Vibrational circular dichroism (VCD) spectra in the mid-infrared region of amino acid films are reported here for the first time. Amino acid films are formed from aqueous solutions with alpha-cyclodextrin (CD) serving as the matrix to facilitate the film formation. This film method eliminates the strong interfering water absorption seen in the solution study and makes it easier to measure the VCD in the 1800-1200 cm-1 region. VCD spectra for films of six amino acids, L-alanine, L-proline, L-methionine, Lhistidine, L-phenylalanine, and L-tryptophan, are obtained. For amino acids with low solubility (L-phenylalanine and L-tryptophan), VCD could not be measured in solution, so the film method is the only means of obtaining the VCD spectra for such amino acids. For amino acids with moderate solubility (L-alanine, L-proline, L-methionine, and L-histidine), VCD spectra are also obtained in the solution state and compared with their corresponding spectra in the film state. A good correlation is found between the film and solution spectra for both absorption and VCD. The VCD spectra of L-methionine, L-histidine, L-phenylalanine, and Ltryptophan are reported here in the mid-infrared region for the first time. The present study broadens the application range of the VCD technique and enhances its role in the detection and analysis of biologically important compounds.     

Quantitative nondestructive methods for the determination of ticlopidine in tablets using reflectance near-infrared and Fourier transform Raman spectroscopy

Two different nondestructive spectroscopy methods based on near-infrared (NIR) and Fourier transform (FT) Raman spectroscopy were developed for the determination of ticlopidine-hydrochloride (TCL) in pharmaceutical formulations and the results were compared to those obtained by high-performance liquid chromatography (HPLC). An NIR assay was performed by reflectance over the 850-1700 nm region using a partial least squares (PLS) prediction model, while the absolute FT-Raman intensity of TCL's most intense vibration was used for constructing the calibration curve. For both methodologies the spectra were obtained from the as-received film-coated tablets of TCL. The two quantitative techniques were built using five "manual compressed" tablets containing different concentrations and validated by evaluating the calibration model as well as the accuracy and precision. The models were applied to commercial preparations (Ticlid). The results were compared to those obtained from the application of HPLC using the methodology described by "Sanofi Research Department" and were found to be in excellent agreement, proving that NIR, using fiber-optic probes, and FT-Raman spectroscopy can be used for the fast and reliable determination of the major component in pharmaceutical analysis.     

Fabrication of triple-layered magnetite-hydrogel-gold nanocomposites for biomedical applications

Magnetite-hydrogel-gold nanocomposites with optical-active, thermo-responsive, and magnetism have been prepared by the following consecutive steps. Hydrogel-encapsulated magnetites were first synthesized by the combination of sol-gel reaction and radical polymerization process, and the resulting magnetic hydrogels were subsequently bound with nano-sized Au (1-3 nm) via a molecular linkage of diamine ligand which was covalently bonded to the carboxylic groups on the hydrogel surface. Au seeds anchored on the magnetic hydrogels were further reduced into nano-scale Au layer which induced the distinct red-shift of absorption band into NIR region. The optical properties and surface morphology of the nanocomposites were characterized by UV-vis spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM).     

Thermally Activated Upconversion Near‐Infrared Photoluminescence from Carbon Dots Synthesized via Microwave Assisted Exfoliation

Upconversion near‐infrared (NIR) fluorescent carbon dots (CDs) are important for imaging applications. Herein, thermally activated upconversion photoluminescence (UCPL) in the NIR region, with an emission peak at 784 nm, which appears under 808 nm continuous‐wave laser excitation, are realized in the NIR absorbing/emissive CDs (NIR‐CDs). The NIR‐CDs are synthesized by microwave‐assisted exfoliation of red emissive CDs in dimethylformamide, and feature single or few‐layered graphene‐like cores. This structure provides an enhanced contact area of the graphene‐like plates in the core with the electron‐acceptor carbonyl groups in dimethylformamide, which contributes to the main NIR absorption band peaked at 724 nm and a tail band in 800–850 nm. Temperature‐dependent photoluminescence spectra and transient absorption spectra confirm that the UCPL of NIR‐CDs is due to the thermally activated electron transitions in the excited state, rather than the multiphoton absorption process. Temperature dependent upconversion NIR luminescence imaging is demonstrated for NIR‐CDs embedded in a polyvinyl pyrrolidone film, and the NIR upconversion luminescence imaging in vivo using NIR‐CDs in a mouse model is accomplished.     

Noninvasive alcohol testing using diffuse reflectance near-infrared spectroscopy

A diffuse reflectance near-infrared (NIR) spectrometer was evaluated as a noninvasive alternative to breath and blood measurements for in vivo alcohol testing. A hybrid partial least squares (PLS) calibration was constructed using a combination of in vivo and in vitro spectral data. This model was subsequently evaluated for its performance in quantifying alcohol concentrations in vivo using a prospective validation study involving subjects who did not participate in the calibration. The validation study entailed induction of alcohol excursions in ten human subjects and comparison of the noninvasive NIR alcohol measurements to blood and breath alcohol measurements. Blood and breath alcohol measurements were performed at the time of each noninvasive NIR measurement (N = 372), establishing the noninvasive NIR measurement standard error relative to blood alcohol at 4.9 mg/dL (0.0049%). Assessment of the hybrid calibration model's sensitivity and selectivity provided strong evidence that the hybrid calibration yielded measurements that were both sensitive to alcohol and independent of other absorbing analytes in human tissue.     

Determining water content in human nails with a portable near-infrared spectrometer

The water content of human nail plates was determined using a portable near-infrared (NIR) spectrometer with an InGaAs photodiode array detector. NIR diffuse reflectance (DR) spectra were collected from 108 cut nail plates with different relative humidity and in vivo from fingernails. Partial least-squares (PLS) regression was applied to the NIR spectra in the 1115-1645 nm region to develop calibration models that determine the water content in the cut nail plates and fingernails. A good correlation was obtained between the NIR spectra and the water content measured by nuclear magnetic resonance (NMR) for the NIR measurement of both cut nail plates and fingernails. The results indicate that the water content in the nails can be determined very rapidly (1 s) by means of the portable NIR spectrometer and PLS regression.     

Internal multiple-scattering hole-enhanced Raman spectroscopy: improved backscattering Fourier transform Raman sampling in pharmaceutical tablets utilizing cylindrical-conical holes

The benefits of Raman signal enhancement and improved measurement precision are demonstrated using 180° backscattering Fourier transform Raman (FT-Raman) spectroscopy from drilled cylindrical-conical holes within pharmaceutical tablet cores. Multiple scattering of the incident laser light within the holes results in an increased Raman signal due to the larger Raman sampling volume. This is important for overcoming typical sub-sampling issues encountered when employing FT-Raman backscattering of heterogeneous pharmaceutical tablets. Hole depth and diameter were found to be important experimental parameters and were optimized to yield the greatest signal enhancement. The FT-Raman spectra collected using backscattering from cylindrical-conical holes is compared to typical 180° backscattering from flat surfaces using tablet cores of Excedrin? and Vivarin?. Raman chemical images are used to establish a representative sampling area. We observe a three- to five-fold increase in the Raman intensity and a two-fold improvement in the measurement precision when sampling from cylindrical-conical holes rather than classic backscattering from flat tablet cores. Self-absorption effects on analyte band ratios are negligible in the fingerprint region but are more significant at the higher near-infrared (NIR) absorbances found in the C-H/O-H/-N-H stretching region. The sampling technique will facilitate developing quantitative FT-Raman methods for application to pharmaceutical tablets using the fingerprint spectral region.     

Near infrared spectroscopy patents for the physicochemical characterization of nanomaterials: the road from production to routine high-throughput quality control

The measurement of the physical and chemical ("physicochemical") properties of nanomaterials used in industry and science including chemistry, pharmacy, medicine, toxicology, etc., is time-consuming, expensive and requires a lot of experience of a well trained lab staff. Near-infrared spectroscopy (NIR; 4.000-12.000 cm(-1)), working in the wavelength region with the highest IR energy, allows obtaining multifactorial information of the material under investigation due to the occurrence of a high number of combination and overtone vibrations. Coupling of an optimized and well-designed measurement technique with multivariate data analysis (MVA) leads to a non-destructive, fast, reliable and robust novel NIR technique for the fast and non-invasive physicochemical characterization, which is suitable for high-throughput quality control due to the short analyses times of only a few seconds. In the following chapters, the patented basic NIR techniques full-filling these aims are introduced, described, summarized and critically discussed.     

Sensitive detection and identification of organic liquids using the second derivative of surface plasmon resonance near-infrared spectra

Sensitive detection of near-infrared (NIR) spectra of several organic liquids has been carried out by surface plasmon resonance (SPR) NIR spectroscopy. For all the liquids, 50- to 100-fold enhancements of the absorption peaks were obtained in the combination band region 4500-4000 cm(-1) using a gold film with a thickness of 14 nm. The SPR peak shows up as an unnecessary broadband peak or trend in an SPR-NIR spectrum, and it was difficult to separate it from the absorption signals. In order to remove the contribution of SPR from the raw SPR-NIR spectrum, the second-order derivative has been employed. The second derivative of the SPR-NIR spectrum was reasonably comparable to that of the corresponding transmittance spectrum. Two simple algorithms for sample identification from the second-derivative data have been proposed. One is similarity, which directly compares the second-derivative spectrum of an unknown sample with that of a known reference sample. The other is fitness, which is defined as a ratio of the common part of absorption peak wavenumbers of the sample and the reference. Although both methods are unfit for the identification of a minor component in a mixture, a major component can be definitely identified by choosing an informative wavenumber region. It was found that the wavenumber region 4250-4080 cm(-1) is especially useful for the identification of similar molecules such as normal alkanes.     

Application of near-infrared and Fourier transform infrared spectroscopy in the characterization of ligand-induced conformation changes in folate binding protein purified from bovine milk: influence of buffer type and pH

Fourier transform infrared (FT-IR) and near-infrared (NIR) spectroscopy have been applied to detect structural alterations in folate binding protein (FBP) induced by ligation in different buffer types. The amide I region pointed to a beta-sheet to alpha-helix transition upon ligation in acetate and phosphate buffers, and the formation of intermolecular beta-sheet was indicated at pH 5.0, in agreement with a dimerization of FBP taking place at this pH. The ligand-induced changes in the 2100-2300 nm NIR region were significant for FBP in acetate and phosphate buffers of pH 5.0, and the variations were interpreted as secondary structure changes, based on previous assignments of secondary structures to the combination bands in the NIR region. In the case of acetate buffer, variations in the amide combination bands agreed with the amide I analysis, but for the other buffer types some discrepancies were found and explained by side-chain contributions to the NIR, which could reflect the tertiary and quaternary structure differences. NIR spectra of FBP at pH 7.4 and 5.0 revealed contradictory effects on the side chains, reflecting different polymerization events at the two pH values, whereas the amide I region indicated similar changes at the two pH values. Therefore, we suggest that FT-IR and NIR spectroscopy may complement each other, such that the two techniques in combination may give information on all three types of protein conformational changes. While the secondary structure changes are revealed by FT-IR, the tertiary and quaternary structure changes are reflected in the NIR spectra, although the general influence of the latter changes on the NIR spectra remains to be confirmed.     

Enhanced Q-switching performance of magnetite nanoparticle via compositional engineering with Ti3C2 MXene in the near infrared region

In this work,we reported a new strategy to improve the nonlinear saturable absorption performance of magnetite (Fe3O4) nanoparticles (FONPs) via the compositional engineering with the Ti3C2 MXene in the near-infrared (NIR) region.Based on the DFT simulation,the band structures and work function were significantly modified by the Ti3C2 MXene doping.By using the open-aperture Z-scan technology,the nonlinear optical features of the FONPs@Ti3C2 nanocomposite were significantly improved,show-ing the great potential as the saturable absorber in the pulsed laser.With the nanocomposite as the saturable absorber,the passively Q-switched Nd∶GdVO4 lasers emitted much shorter pulse durations when compared with the pristine FONP saturable absorber.These findings indicated that FONPs@Ti3C2 heterostructure was a promising saturable absorber for the short pulse generation in the NIR region.     

Investigation of solid-phase peptide synthesis by the near-infrared multispectral imaging technique: a detection method for combinatorial chemistry.

A near-infrared (NIR) multispectral imaging spectrometer was used to monitor solid-phase peptide synthesis. This imaging spectrometer has fast scanning ability and high sensitivity because it is based on an acousto-optic tunable filter and a NIR InGaAs focal plane array camera. This NIR imaging instrument possesses all the advantages of conventional NIR spectrometers; namely, it can be used for noninvasive monitoring of the reactions and identification of the products during the solid-phase peptide synthesis of glycine, alanine, and valine mediated by aminomethylstyrene resin beads. The reaction was determined by monitoring either the decrease of the band at 1529 nm, which is due to the amine group on the beads, or the increase of the amide band generated at 1483 nm. The amine band at 1529 nm was also used to determine the presence of the Fmoc protecting groups and the efficiency of its removal. More importantly, this NIR imaging spectrometer has additional features that conventional NIR spectrometers cannot offer; namely, its ability to measure spectra at different positions within a sample. This feature was utilized for the first demonstration in which reactions of three different solid-phase peptide syntheses (in a three-compartment cell) were simultaneously monitored. As expected, the kinetics obtained for three reactions are similar to those obtained when the each of the reactions was individually determined. In this study, data recorded by 16 x 16 pixels were used to calculate a spectrum for each sample. However, a relatively good spectrum can be obtained by using data recorded by a single pixel. Since the NIR camera used in this camera is equipped with 240 x 320 pixels, this NIR mutispectral imaging technique is not limited to the three-compartment cell used in this study but rather can be used as the detection method for the solid-phase peptide synthesis in combinatorial chemistry.