News – Dr. John Edwards of Process NMR Associates will be presenting the following 3 posters and invited talk at the 1st Practical Applications of NMR in Industry Conference (PANIC), Schaumburg, IL, October 15-17, 2012

Invited Talk

On-line Applications of 60 MHz High-Resolution NMR Systems in Industry: Direct Measurements, Chemometric Correlations, and Multiple Spectroscopy Data Fusion

John C. Edwards Process NMR Associates, LLC, Danbury, CT

For the past two decades high resolution 1H NMR systems combined with chemometric analyses have been utilized in refineries and chemical plants to predict the chemical and physical properties of process streams and finished products. The ability to perform these analyses with on-line NMR instrumentation has allowed tighter control and optimization of the plant to obtain margin improvement, reduced reworking of off-specification materials, and higher yields of finished products. Examples of refinery and petrochemical applications will be given along with some examples of multinuclear NMR applications utilizing 31P and 19F NMR. The permanent magnet based 1.5 Tesla NMR instruments will be described along with a description of how these compact, cryogen-free NMR systems can be utilized on the bench-top or in the fume-hood as continuous or stop-flow chemistry sensors for reaction monitoring, mixing/dilution monitoring, or purity/conversion monitoring. Food applications will also be described such as dairy (butter, cream cheese) and edible or essential oil analysis. Finally, the ability to improve the quality of the correlations derived in the chemometric modelling by “fusing” NMR data with spectral information from other spectroscopies (NIR, Mid-IR) will be discussed.

Poster 1

1H qNMR Determination of Acetylated Polysaccharides, Glucose, Maltodextrin, Isocitrate, Degradation Products, Preservatives and Additives in Aloe Vera Leaf Juice

John C. Edwards Process NMR Associates, LLC, Danbury, CT

Aloe Vera is a botanical component that is used widely in the cosmetic, natural product, herbal supplement, and pharmaceutical industries. The widespread use of Aloe Vera has lead to the need to adequately analyze the authenticity, quality, and quantity of the various components present in this material. The 1H qNMR method described here was developed and validated by Process NMR Associates for a number of NMR service customers and the method will be included in an upcoming Monograph on Aloe Vera published by the American Herbal Pharmacopoeia. The method can be used for the detection and quantitation of the primary components of interest in Aloe Vera juice products and raw materials for compliance with IASC (International Aloe Science Council) certification requirements, specifically, for determination of the content of acetylated polysaccharides, the presence of glucose, the presence and content of maltodextrin, and the content of isocitrate. Additionally, for meeting quality control specifications beyond IASC requirements, the presence and content of the following groups of compounds can be determined: degradation products (e.g., lactic acid, pyruvic acid, succinic acid, fumaric acid, acetic acid, formic acid, and ethanol), preservatives (e.g., potassium sorbate, sodium benzoate, and citric acid/citrate), and other atypical impurities, additives, or adulterants (e.g., methanol, glycine, glycerol, sucrose, maltodextrin, flavorants (propylene glycol/ethanol)). We will describe a common internal-standard NMR methodology that does not require additional equipment or advanced automation software. The method is applicable to a number of different Aloe Vera raw materials and products, including liquid and dried juices. In aloe vera finished products the method is only applicable when the observable aloe vera constituents are present at a high enough concentration to be observed and are not obscured by additional product ingredients with signals in overlapping areas.

Poster 2

Compact, Cryogen-Free, High-Resolution 60 MHz Permanent Magnet NMR Systems for Reaction Monitoring and On-Line/At-Line Process Control Observing 1H, 19F, 31P

John C. Edwards1, Tal Cohen2, Paul J. Giammatteo1

1. Process NMR Associates, LLC Danbury, CT
2. Aspect AI, Shoham, Israel

A compact high resolution NMR system will be described that can be situated on the bench-top or in the fume hood to be used as a continuous or stop-flow detector and/or an “in-situ” reaction monitoring system. The same system can be fully integrated into on-line shelters for on-line process control or utilized by engineers and technicians in an “at-line” environment. The system uses a unique 1.5 Tesla permanent magnet that can accommodate sample tube diameters of 3-10 mm with half-height spectral resolution (water resonance) approaching 1-3 Hz depending on the sample volume size and with excellent single pulse sensitivity. These systems can be utilized in a traditional NMR methodology approach or combined with chemometric approaches that allow NMR data to predict chemical and physical properties of materials via regression analyses that establish correlations between observed spectral variability and sample-to-sample property variance [1].

1) “Process NMR Spectroscopy: Technology and On-line Applications”, John C. Edwards, and Paul J. Giammatteo, in Process Analytical Technology: Spectroscopic Tools and Implementation Strategies for the Chemical and Pharmaceutical Industries, 2nd Ed., Editor Katherine Bakeev, Blackwell-Wiley, 2010

Poster 3

Calculation of Average Molecular Descriptions of Heavy Petroleum Hydrocarbons by Combined Analysis by Quantitative 13C and DEPT-45 NMR Experiments

John Edwards Process NMR Associates, LLC, Danbury, CT

Much debate has centered around the validity and accuracy of NMR measurements to accurately describe the sample chemistry of heavy petroleum materials. Of particular issue has been the calculated size of aromatic ring systems that in general seem to be underestimated in size by NMR methods. This underestimation is principally caused by variance in chemical shift ranges used by researchers to define the aromatic carbon types observed in the 13C NMR spectrum, in particular the bridgehead aromatic carbons that can be shown to overlap strongly with the protonated aromatic carbons. The ability to discern between bridgehead aromatic carbons and protonated carbons in the 108-129.5 ppm region of the spectrum is key in the derivation of molecular parameters that describe the “molecular average” present in the sample. Utilizing methodologies developed by Pugmire and Solum for the solid-state 13C NMR analysis of coals and other carbonaceous solids we have developed a new liquid-state 13C NMR method that allows the relative quantification of overlapping protonated and bridgehead aromatic carbon signals to be determined. The NMR experiments involve the combined analysis of both quantitative 13C single pulse excitation which observes all carbons quantitatively, and a DEPT45 polarization transfer which observes only the protonated carbons in the sample. Though the DEPT45 results are not quantitative across all carbon types (CH, CH2, and CH3) due to polarization transfer differences, the technique is well enough understood that simple multiplication factors allow the relative intensities of the different carbons to be determined. The average ring system sizes derived from these NMR experiments tend to be several ring systems larger than has been calculated in previous studies. In heavy petroleum asphaltenes the average aromatic ring system is 5-7 rings in size which is in agreement with FTICR-MS and fluorescence measurements, rather than the 3-4 rings previously reported.

News – John Edwards of Process NMR Associates will be presenting the following 3 posters at SMASH NMR Conference, Providence RI, September 9-12, 2012. Process NMR Associates will also have a vendor table where John will be available to discuss the exciting range of high and low resolution permanent magnet NMR products available through the company and it’s partners Aspect AI and Cosa-Xentaur.

Poster 1
Quantitative Proton Nuclear Magnetic Resonance Spectrometry (1H-NMR) for Determination of Acetylated Polysaccharides, Glucose, Maltodextrin, and Isocitrate in Aloe Vera Leaf Juice

John C. Edwards, Process NMR Associates, Danbury, Connecticut

Aloe Vera is a botanical component that is used widely in the cosmetic, natural product, herbal supplement, and pharmaceutical industries. The widespread use of Aloe Vera has lead to the need to adequately analyze the authenticity, quality, and quantity of the various components present in this material. The qNMR method described here was developed and validated by Process NMR Associates (Danbury, CT) and is similar to an independently validated method developed by Jiao et al [1]. The method described is to be included in an upcoming Monograph on Aloe Vera published by the American Herbal Pharmacopoeia. The method can be used for the detection and quantitation of the primary components of interest in Aloe Vera juice products and raw materials for compliance with IASC (International Aloe Science Council) certification requirements, specifically, for determination of the content of acetylated polysaccharides, the presence of glucose, the presence and content of maltodextrin, and the content of isocitrate. Additionally, for meeting quality control specifications beyond IASC requirements, the presence and content of the following groups of compounds can be determined: degradation products (e.g., lactic acid, pyruvic acid, succinic acid, fumaric acid, acetic acid, formic acid, and ethanol), preservatives (e.g., potassium sorbate, sodium benzoate, and citric acid/citrate), and other atypical impurities, additives, or adulterants (e.g., methanol, glycine, glycerol, sucrose, maltodextrin, flavorants (propylene glycol/ethanol)). We will describe a common internal-standard NMR methodology that does not require additional equipment or advanced automation software. The method is applicable to a number of different Aloe Vera raw materials and products, including liquid and dried juices. In aloe vera finished products the method is only applicable when the observable aloe vera constituents are present at a high enough concentration to be observed and are not obscured by additional product ingredients with signals in overlapping areas.

1. “Quantitative 1H-NMR spectrometry method for quality control of Aloe vera products”, Jiao, P., Jia, Q., Randel, G., Diehl, B., Weaver, S., Milligan, G., J AOAC Int., 93(3), 842-848, 2010

Poster 2
Practical Applications of Compact, Cryogen-Free High-Resolution 60 MHz Permanent Magnet NMR Systems for Reaction Monitoring and Online/At-Line Process Control

John C. Edwards, Process NMR Associates, LLC, 87A Sand Pit Road, Danbury, CT 06810 USA

For the past two decades high resolution 1H NMR at 60 MHz has been utilized to monitor the chemical physical properties of refinery and petrochemical feedstreams and products1. These approaches involve the use of partial least squares regression modelling to correlate NMR spectral variability with ASTM and other official test methods, allowing the NMR to predict results of physical property tests or GC analysis. The analysis is performed in a stop flow environment where solenoid valves are closed at the beginning of the NMR experiment. This approach allows up to 5 or 6 different sample streams to be sent to the sample in order to maximize the impact of the instrument. The current work with these permanent magnet NMR systems is to utilize them as chemistry detectors for bench-top reaction monitoring, mixing monitoring, dilution monitoring, or conversion monitoring. In the past use of NMR for these applications has been limited by the need to bring the “reaction” to the typical “superconducting” NMR lab. A compact high resolution NMR system will be described that can be situated on the bench-top or in the fume hood to be used as a continuous or stop-flow detector and/or an “in-situ” reaction monitoring system. The system uses a unique 1.5 Tesla permanent magnet that can accommodate sample diameters of 3-10 mm with half-height resolution approaching 1-3 Hz (depending on the sample size) and excellent single pulse sensitivity. Reaction monitoring can be performed using a simple flow cell analyzing total system volumes of 2 to 5 mL depending on the length and diameter of the transfer tubing. Further, detection limits of analytes in the 200+ ppm range are possible without the use of typical deuterated NMR solvents. Analysis times of 5 to 20 seconds are also possible at flow rates of 5 to 20+ ml/minute. Reaction monitoring directly in standard 5-10 mm NMR tubes using conventional (non-deuterated) reactants, solvents and analytes will also be described. Examples of 1H, 19F and 31P analyses will be described.

1.“Process NMR Spectroscopy: Technology and On-line Applications” John C. Edwards, and Paul J. Giammatteo, in Process Analytical Technology: Spectroscopic Tools and Implementation Strategies for the Chemical and Pharmaceutical Industries, 2nd Ed., Editor Katherine Bakeev, Blackwell-Wiley, 2010

Poster 3
Calculation of Average Molecular Descriptions of Heavy Petroleum Hydrocarbons by Combined Analysis by Quantitative 13C and DEPT-45 NMR Experiments

John C. Edwards

Process NMR Associates, LLC, 87A Sand Pit Rd, Danbury, CT 06810 USA

Over the years much debate has centered around the validity and accuracy of NMR measurements to accurately describe the sample chemistry of heavy petroleum materials. Of particular issue has been the calculated size of aromatic ring systems that in general seem to be underestimated in size by NMR methods. This underestimation is principally caused by variance in chemical shift ranges used by researchers to define the aromatic carbon types observed in the 13C NMR spectrum, in particular the bridgehead aromatic carbons that can be shown to overlap strongly with the protonated aromatic carbons. The ability to discern between bridgehead aromatic carbons and protonated carbons in the 108-129.5 ppm region of the spectrum is key in the derivation of molecular parameters that properly describe the “molecular average” present in the sample. Utilizing methodologies developed by Pugmire and Solum [1] for the solid-state 13C NMR analysis of coals and other carbonaceous solids we have developed a new liquid-state 13C NMR method that allows the relative quantification of overlapping protonated and bridgehead aromatic carbon signals to be determined [2]. The NMR experiments involve the combined analysis of both quantitative 13C single pulse excitation which observes “all carbons in the sample” and DEPT45 polarization transfer which observes only the protonated carbons in the sample. Though the DEPT45 results are not quantitative across all carbon types (CH, CH2, and CH3) due to polarization transfer differences, the technique is well enough understood that simple multiplication factors allow the relative intensities of the different carbons to be determined. An additional aspect of the experiments is the addition of a standard material (PEG polymer) that allows the calculation of the absolute percentage of the carbons observed by the NMR technique. This allows the relative amount of bridgehead carbon to be calculated by direct comparison of the aromatic region with the standard signal intensity. The average ring system sizes derived from these NMR experiments tend to be several ring systems larger than has been calculated in previous studies. In asphaltenes for example the ring systems are 5-7 rings in size rather than the 3-4 rings reported previously. The ring sizes determined by this new combined NMR method are in agreement with FTICR-MS and fluorescence measurements.

1) “Carbon-13 Solid-State NMR of Argonne Premium Coals”, Mark S. Solum, R.J. Pugmire, David M. Grant, Energy Fuels, 1989, 3(2), pp 187-193

2)” Comparison of Coal-Derived and Petroleum Asphaltenes by 13C Nuclear Magnetic Resonance, DEPT, and XRS”, A. Ballard Andrews, John C. Edwards, Andrew E. Pomerantz, Oliver C. Mullins, Dennis Nordlund, and Koyo Norinaga, Energy Fuels, 2011, 25 (7), pp 3068–3076