Using Compact ¹H NMR, NIR, and Raman Spectroscopy Combined with Multivariate Data Analysis to Monitor a Biocatalyzed Reaction in a Microreaction System

Abstract

Process analytical technology aims at process knowledge and process improvement, efficiency, and sustainability. A prerequisite is process monitoring. The combination of microreaction systems and spectroscopy proved suitable due to dimension and compound reduction and real-time monitoring capabilities. Compact 1H NMR, NIR, and Raman spectroscopy were used to monitor the biocatalyzed hydrolysis and esterification of acetic anhydride to isoamyl acetate using immobilized Candida antarctica lipase B (CALB) in a microreaction system in real-time. To facilitate the identification of signals suitable for the extraction of concentration-time (c-t) graphs, 2D heterocorrelation spectra were generated through covariance transformations applied to 1D Raman, NIR, and NMR data. By means of this purely mathematical statistical procedure, the relevant signals of the process media were assigned to educts and products and thus made applicable for univariate data evaluation. The data obtained were interpreted in terms of a first-order kinetic model, and corresponding reaction rate constants were extracted. An alternative, elegant, and fit-for-automation approach for the kinetic analysis of the spectra was demonstrated in using multivariate curve resolution (MCR). The results of the univariate and multivariate approaches were comparable with regard to reaction rates and concentrations. While the manual integration of the 1H NMR spectra followed by univariate analysis allowed to establish a concentration profile of the final product isoamyl acetate hence revealing more details, multivariate analysis was found more suitable for process automation.

Vibrational Fingerprint of Erlotinib: FTIR, RS, and DFT Studies

“…Bond length (Å) Bonds Angle (°) Bonds Dihedral angle (°) C 1 -C 2 1.204 C 2 -C 3 -C 8 119.5 C 6 -C 7 -N 9 -C 10 − 179.3 C 2 -C 3 1.430 C 8 -C 7 -N 9 124.5 N 9 -C 10 -C 11 -C 12 1.071 C 3 -C 4 1.403 N 9 -C 10 -N 19 120.0 C 11 -C 12 -C 13 -O 20 174.9 C 4 -C 5 1.390 N 9 -C 10 -C 11 118.8 C 16 -C 15 -C 14 -O 25 − 179.1 C 5 -C 6 1.388 C 10 -C 11 12 1.414 C 15 -C 14 -O 25 125.0 C 12 -C 13 1.374 C 14 -O 25 -C 26 118.9 C 13 -C 14 1.433 O 25 -C 26 -C 27 108.4 C 14 -C 15 1.378 C 26 -C 27 -O 28 109.4 C 15 -C 16 1.414 C 27 -O 28 -C 29 112.8 C 16 -N 17 1.367 N 17 -C 18 1.310 C 18 -N 19 1.351 N 19 -C 10 1.323 C 11 -C 16 1.418 C 13 -O 20 1.364 O 20 -C 21 1.441 C 21 -C 22 1.519 C 22 -O 23 1.418 O 23 -C 24 1.412 C 14 -O 25 1.356 O 25 -C 26 1.428 C 26 -C 27 1.511 C 27 -O 28 1.412 O 28 -C 29 1.414…”

“…ese studies present vibrational spectroscopy characterization by means of Raman spectroscopy (RS) and Fourier-transform infrared absorption spectroscopy (FTIR) of the molecular structure of erlotinib in the solid state and solution in different pH conditions. ese two complementary methods are commonly used for qualitative and quantitative analysis of different types of samples in various conditions and physical states [10][11][12][13][14][15]. RS and FTIR are governed by different quantum mechanical selection rules [16].…”

Direct monitoring of biocatalytic deacetylation of amino acid substrates by 1H NMR reveals fine details of substrate specificity

“…33 Given the various advantages of 1 H NMR spectroscopy, such as the easy analysis set-up, short measurement time, direct structural information, high accuracy and its non-destructive nature, this technique had already been applied for the quantitative analysis of active ingredients (AI), natural products and complex biological mixtures. 33,34 Furthermore, 1 H NMR spectroscopy has been used to measure biocatalysed reactions; examples include lipase-catalysed acylations 35 and monophosphates ring opening reactions, 36 determination of the % ee of hydrolytic KRs, 37,38 and to characterise complex carbohydrate derivatives. 39,40 Here we report the development, optimization and application of a novel 1 H NMR assay to monitor amide hydrolysis catalysed by a highly active deacetylase (Scheme S1D †).…”

Determination of the Mono and Dibromo Derivatives Ratio Resulting from Semiconductor Bromination Using Ultraviolet-visible Absorption Spectroscopy and Gaussian Peak Fitting

“…Meanwhile, due to cost efficient concern in industrial production, approaches of quantitative analysis of the composition ratio of reaction systems that are convenient and inexpensive were wildly studied. [1][2][3][4][5] Conventional quantitative analysis methods include Gas/liquid chromatography, 6,7 Nuclear magnetic resonance, 8 Raman spectroscopy, 9 Ultraviolet-visible (UV-Vis) absorption spectroscopy, [10][11][12][13] etc. Among these methods, the cost of UV-Vis absorption spectroscopy is quite low, because the equipment itself is less pricey then others, and relatively easier to maintain or operate.…”