John C Edwards - Profile on Academia.edu (original) (raw)

Papers by John C Edwards

Average Molecular Structure of Gasoline Engine Combustion Chamber Deposits Obtained by Solid-State 13 C, 31 P, and 1 H Nuclear Magnetic Resonance Spectroscopy

SAE Technical Paper Series, 1993

Journal of Food Research, 2014

FruiteX-B ® -calcium fructoborate (FrxB) plant mineral complex was investigated in this study. Al... more FruiteX-B ® -calcium fructoborate (FrxB) plant mineral complex was investigated in this study. Although calcium fructoborate is naturally-occurring and found in commonly ingested fruits and vegetables, the commercially produced FrxB calcium fructoborate complex is formed by a proprietary reaction of boric acid with fructose and calcium carbonate. Liquid and solid-state 13 C and 11 B NMR were utilized in order to establish a baseline standard of FrxB for product quality purposes, to establish a reliable methodology to positively identify and quantify amounts of FrxB present in tablets and capsules, liquids and powdered blends wherein the FrxB may have been mixed with other ingredients, excipients, or adulterants such as maltodextrin or magnesium stearate, and to establish a robust and reliable testing method for the identification and quantification of the mono-and the di-complexes of calcium fructoborate as well as any free borate and/or free fructose that may be present. The molar ratio of the various components of calcium fructoborate was studied by 11 B and 13 C NMR in order to establish the relative amounts of free borate, free fructose, and mono-ester/di-ester complex present in the material. A quantitative 11 B NMR method was developed to enable quantification of the amount of FrxB present in products wherein it had been tableted or encapsulated in combination with other dietary supplement ingredients, or excipients such as magnesium stearate or maltodextrin. A quantitative 13 C NMR method was developed to quantify free fructose content in the complex. Finally, an NMR based product stability study was performed to monitor molecular level stability of the complex at temperatures ranging from 35-70 ºC with exposures lasting from 2-18 hours.

SAE Technical Paper Series, 2010

African and global vehicle parcs. South Africa is in a unique position because a significant port... more African and global vehicle parcs. South Africa is in a unique position because a significant portion of all liquid fuels consumed are synthetically produced from coal and gas. These fuels are mainly supplied into the inland regions, particularly the Gauteng province, the economic heartland of South Africa and the most densely populated area in the country. It is important to understand the performance of synthetic fuels in the latest generation engines, in order to ensure that these fuels are fit for use in these new applications. The latest generation DISI gasoline engines (also known as Gasoline Direct Injection™ and Fuel Stratified Injection™) differ significantly in operation to older Port Fuel Injected (PFI) engines.

Over the past few years our analytical NMR service has been developing a detailed chemical finger... more Over the past few years our analytical NMR service has been developing a detailed chemical fingerprint analysis of alcoholic beverages by quantitative 1 H NMR (qHNMR). Beyond the typical analyses of beer, wine, port, hard cider, sake and spirits, we have been looking at other fermented beverages such as kombucha, kefir, kvass, mead, alcoholic ginger beer, alcoholic root beer, and perry. As well as the final fermented beverage products, we have been actively investigating the various starting materials such as malt wort, apple juice, honey, grape juice, fruit juices, tea, and coffee. The NMR analysis can provide a rapid quantitative analysis without any sample preparation based on the molar ratio of integration value of unique molecular fingerprint peaks with the integrated signal of an internal standard. In our case we typically use maleic acid as an internal standard as it's singlet signal peak appears in a non-overlapping area of the spectrum compared to the chemistry we are interested in following. The information that can be derived from the NMR experiment covers a wide dynamic range of component molecule concentrations from 10-100,000 ppm. The analysis observes all fully dissolved chemical constituents and the spectral response is linear with regard to all chemical types. As a primary analytical method the chemist or brewer can utilize the well understood literature on the NMR chemical shifts and couplings that allow first principle analysis of each molecular fingerprint to identify and quantify the presence of targeted and non-targeted molecules in the complex mixture. The analysis provides quantitative information on the following chemical components: ethanol, higher (C3,C4,, maltose, 1,6-and 1,4-dextrin chemistry, maltotriose, lactose), polyphenols. It can also provide information on yeast metabolism products such as 2,3-butandiol (directly from Enterobacter activity or from the action of saccharomyces on diacetal which is a well-known beer flavor deviation), 1,3-propandiol (from yeast action on glycerol after carbohydrates have been entirely fermented from the beverage). In recent years kombucha has been found to contain more than 0.5% v/v ethanol. This fact could lead them to be classified as alcoholic beverages and bring the product under scrutiny and taxation by the Alcohol and Tobacco Tax and Trade Bureau which federally regulates the alcoholic beverage industry. Kombucha is a sweetened black or green tea that has been inoculated with a symbiotic culture of bacteria and yeast (SCOBY) which ferments in both the manufacturing process and in the bottle during the shipment and shelf life of the product. The drink is sold under the premise that the SCOBY, and the fermented drink, provide a probiotic culture to the consumer. In order to maintain an active probioic product the acitivity of the culture is not arrested by pasteurization or by addition of sorbate at the end of the fermentation stage. The kombucha is bottled with active SCOBY present in a sugar containing tea drink. Fermentation is then thought to occur during shipment, distribution and while the product sits on shelves leading to a final alcohol content greater than0.5% ABV when the drink is purchased and consumed. We have utilized 1 H NMR to obtain quantitative ethanol concentrations on a number of kombucha beverages bought off the shelf at grocery stores. The samples we analyzed represent the entire dataset of kombuchas that we purchased and they represent the products of 5 different manufacturers. We also aged two of the products at room temperature for 7 months and analyzed them to observe the effect of long term aging on kombucha products. We also quantitatively analyzed the sample for various organic acid concentrations as well as residual sugars.

A Review of Applications of NMR Spectroscopy in the Petroleum Industry

Spectroscopic Analysis of Petroleum Products and Lubricants, 2011

Relationship Between Combustion Chamber Deposits, Fuel Composition, and Combustion Chamber Deposit Structure

SAE Technical Paper Series, 1993

Environmental Science & Technology, 1996

1H quantitative NMR (qNMR) has been utilized to assess the the small molecule and carbohydrate ch... more 1H quantitative NMR (qNMR) has been utilized to assess the the small molecule and carbohydrate chemistry of a number of home-brewed and commercial alcoholic ciders. A quantitative chemistry distribution of the products of the various fermentations that occur in cider making. Malolactic fermentation as well as fermentation by saccharomyces and wild yeasts occur in the cider making process which traditionally occurred without the intentional addition of yeast by the manufacturer. The distribution of small molecules produced by the yeast and bacterial metabolomes at work in the process can yield information of the sensory perception of ciders produced in different ways. An investigation of the residual sugar chemistry of commercial ciders gives some indication of the process of sweetening commercial cider products with sugar additions after fermentation is complete. These typical commercial ciders are very different in chemistry distribution compared to very dry cider styles such as those found in the Basque region of Spain where fermentation is taken to the extreme resulting in complete conversion of sugars to alcohol but also glycerols to 1,3 propandiol. Finally it was decided to determine how much quantitative chemistry information could be obtained from benchtop NMR systems operating in the 60 MHz range. These benchtop NMR systems have a price and cost-of-ownership that would allow small laboratories of manufacturers to think about their use in QA and QC roles.

Benchtop high-resolution NMR systems are available at a number of field strengths and probe confi... more Benchtop high-resolution NMR systems are available at a number of field strengths and probe configurations. However beyond the obvious academic instruction market for these instruments very few applications have been demonstrated across all available platforms and thus proving the general applicability of benchtop NMR technology to industrial quality control. We will present two chemometric-based applications that have been developed at 4 different field strengths utilizing Varian Mercury 300 MHz, Magritek Spinsolve 42 MHz, Aspect AI 60 MHz, and Thermo Picospin 80 MHz NMR systems. Partial-least-squares (PLS) regression correlations were obtained on all 4 platforms relating to:

Omega-3 fatty acid composition of samples taken from various points in a nutritional supplement manufacturing process. Excellent correlations were obtained on all 4 NMR instruments proving that NMR technology is applicable to in-lab, at-line. or on-line analysis of fish oil derived omega-3 fatty acid supplements. The 40 second NMR analysis effectively replaces a 60+ minute GC analysis.
Physical and chemical property determination of diesel fuels where excellent correlations were obtained between 1H NMR variability and parameters such as density, aromatic content by GC, hydrogen content by 1H TD-NMR (ASTM D7171 method), and sulfur content. Many more physical and chemical properties can be correlated to the 1H NMR spectrum allowing a single 40 second NMR experiment to predict 10-15 parameters that each require dedicated analyzers.
Finally, we will present the concept and initial results from an independent server-based NMR application software that can be utilized in conjunction with the NMR software of the current benchtop NMR systems, or alternatively as a stand-alone application platform. This software would effectively make chemometric and direct measurement NMR application ubiquitous across all NMR platforms.

The adulteration of dietary supplements (or natural health products) with synthetic pharmaceutica... more The adulteration of dietary supplements (or natural health products) with synthetic pharmaceuticals is an area of increasing concern, which presents substantial risk to public health. Widely available in retail and via the Internet, these products are often marketed as sexual enhancement, weight loss and/or bodybuilding supplements. Unlike prescription drugs, supplements do not require premarket approval by FDA before they are made available for public consumption. In fact, the agency can only take investigational action after the adulterated product has caused harm and the adverse event has been reported via MedWatch (FDA’s online portal for voluntary reporting of adverse events associated with drugs, medical devices and dietary supplements).
Development of analytical tools for screening and identification of adulterated products in the marketplace represents a significant step forward in the fight against adulterated dietary supplements. Several organizations, including AOAC and USP, have undertaken initiatives to evaluate and recommend analytical methodologies for screening supplements for adulteration. HPLC and mass spectrometry have so far dominated the screening and quantitation studies published in the literature, with NMR spectroscopy often relegated to the status of structure elucidation tool. In this work, we investigate the ability of several-low field NMR spectrometric platforms to successfully identify and quantify the presence of adulterating drug substances in sexual enhancement and weight loss supplements purchased online and in US retail. 1H qNMR of both types of samples was performed with 300 MHz NMR to confirm the presence of adulterants such as sildenafil, tadalafil, and their structural analogues (sexual enhancement supplements) and various synthetic stimulants (weight loss supplements). We have concluded that a simple sample preparation protocol combined with straightforward 1H NMR spectroscopic analysis yields a rapid, robust and reliable screening test for adulterated supplements, presenting an attractive alternative to more labor-intensive, expensive and expertise-demanding techniques du jour.

Multinuclear liquid and solid-state NMR spectroscopy was capable of defining the fructoborate str... more Multinuclear liquid and solid-state NMR spectroscopy was capable of defining the fructoborate structure, and allowed identification of the pure complex as well as Quantitation of Fruitex-B product in the presence of excipient and adulterants.

Aluminum (Al) is the third most abundant element and the most abundant element found in the Earth... more Aluminum (Al) is the third most abundant element and the most abundant element found in the Earth's crust. Elemin™ (FutureCeutical, Inc., Momence, IL, USA) is a multi inorganic element complex with more then 70 inorganic elements and minerals all of which are completely water soluble, including all the Al compounds. The objective of this study is to show, using NMR technology, that Al compounds present in an aqueous solution of Elemin™ are almost exclusively soluble sulphate forms and confirm that they are not present as insoluble forms such as Al oxide or Al hydroxide. We have obtained liquid and solid-state 27 Al NMR spectra for Elemin™ and several model salts such as Al 2 (SO 4 ) 3 , KAl(SO 4 ) 2 , Al 2 O 3 and Al(OH) 3 .

For the past decade it has been well documented that many over-the-counter dietary supplement pro... more For the past decade it has been well documented that many over-the-counter dietary supplement products that claim to enhance sexual performance are in fact adulterated with undeclared phosphodiesterase type 5 (PDE5) inhibitors 1 . Examples of these PDE5 inhibitors are sildenafil (Viagra®) and tadalafil (Cialis®) and a large number of analog materials. In a recent "raid" by Pfizer Global Security which obtained 91 products from convenience stores and filling stations in two U.S. metropolitan areas, it was found that 81% of the products (74) were adulterated with PDE5 inhibitors 2 . HPLC, NMR, and mass spectrometry have dominated screening and quantitation studies that have been reported in the literature 3-6 . Initiatives are under way under the auspices of AOAC and USP to establish the appropriate analytical methodologies to identify adulterated products. Adulterants are usually present at dosages typical of Viagra® (25-100 mg) and Cialis® (5-20 mg). The drug, or an analog, is customarily spray dried onto the herbal substrate. In order to avoid detection, adulterators have even been known to incorporate the drug material into the capsule shell itself. In this study, we investigated the ability of low field NMR (60 MHz) to identify and quantify PDE5 inhibitors in a number of over-the-counter products sold as sexual enhancement supplements. 1 H qNMR of a series of herbal supplements was performed on a 300 MHz NMR, as well as on a bench-top 60 MHz NMR, in order to determine the presence of drug adulteration by PDE5 inhibitors such as sildenafil, tadalafil, and their synthetic analogues. It was determined that simple sample preparation techniques (extraction with CD 3 CN or CD 3 CN/D 2 O) are adequate, and subsequent 1 H NMR analysis can yield a rapid screening test. Identification of PDE5 inhibitors was found to be plausible from both the 60 and 300 MHz NMR data. Quantification by internal standards was also readily performed. Though the 300 MHz instrument yielded higher resolution spectra that were easier to assign in the aliphatic region, it was the aromatic proton region of the spectrum that allowed an easy direct spectral fingerprint comparison to be performed across magnetic field strengths.

The molecular architecture of asphaltenes is still a matter of debate. Some literature reports pr... more The molecular architecture of asphaltenes is still a matter of debate. Some literature reports provide evidence that the contrast of petroleum asphaltenes versus coal-derived asphaltenes is useful for understanding the governing principles of asphaltene identity. Coal-derived asphaltenes provide an excellent test for understanding the relationship of asphaltene molecular architecture with asphaltene properties. Diffusion measurements have shown that coal-derived asphaltenes are half the size of many crude oil asphaltenes, but there are relatively few studies comparing coal-derived and petroleum asphaltenes using liquid state 13 C NMR. 13 C NMR confirms that the molecular sizes of these coal-derived asphaltenes are smaller than virgin petroleum asphaltenes. DEPT-45 experiments were performed in order to determine the relative amount of nonprotonated and protonated carbon in the aromatic region of the spectrum. In contrast to previous NMR work on asphaltenes that ignored interior bridgehead carbon, we show this is an important component of asphaltenes and that correctly accounting for this carbon enables proper determination of the number of fused rings. XRS data supports interpreting the NMR data with a model that weighs circularly condensed structures more heavily than linearly condensed structures. Significantly more carbon exists in chains at least 9 carbons long in petroleum asphaltenes (g7%) compared to coal-derived asphaltenes (g1%). .

Carbon, 2010

A large number of solid-state NMR and ESR experiments were explored as potential tools to study c... more A large number of solid-state NMR and ESR experiments were explored as potential tools to study chemical structure, mobility, and pore volume of activated carbon. We used a model system where pecan shells were activated with phosphoric acid, and carbonized at 450°C for 4 h with varying amounts of air flow. Through the use of different NMR experiments (e.g., CP-MAS, SPE-MAS, and DD-MAS) several structural parameters were calculated such as mole fraction of bridgehead aromatic carbons, number of carbons per aromatic ring system, and number of phenolic carbons per aromatic ring system. The relaxation time measurements (T 1 , T CH , and T H 1q ) were indicative of the relative mobility of different structural units. ESR spectra showed the presence of p-type aromatic free radicals in the carbonized samples with a slight shift in g value with increasing oxidation. The combined NMR and ESR data give a consistent picture of the carbon structure and the carbonization process, which is not easily available otherwise. In addition, the 1 H NMR data on adsorbed water are shown to be consistent with the trends in the amount of pore volumes for different samples of activated carbons.

Macromolecules, 2003

Mayo plots have been used to determine the rate constant ktr for chain transfer catalysis by (C5P... more Mayo plots have been used to determine the rate constant ktr for chain transfer catalysis by (C5Ph5)Cr(CO)3 • of the AIBN-initiated polymerization of MMA from 60 to 80°C. The value of ktr decreases with temperature, implying that abstraction of H • from the chain-carrying radical by (C5Ph5)Cr(CO)3 • does not occur in a single step and suggesting the associative formation of a caged radical pair. No CIDNP is observed for the reaction of (C5Ph5)Cr(CO)3H with MMA.

Applied Catalysis A-general, 1999

Three classes of inorganic solid acid catalyst have been demonstrated to be effective for methyl ... more Three classes of inorganic solid acid catalyst have been demonstrated to be effective for methyl tert-butyl ether (MTBE) syntheses from methanol/tert-butanol (TBA) feed mixtures using a continuous, plug-¯ow, reactor system. These catalysts include heteropoly acids, such as 12-tungstophosphoric acid and 12-molybdophosphoric acid, on Group III and IV oxide supports, such as titania, HF-treated montmorillonite clays, as well as mineral acid-activated clays. Changes in the structure of the 12-tungstophosphoric acid-on-titania during etheri®cation service have been investigated using 31 P and 1 H MAS NMR.

Molecular composites: design of inclusion complexes of polyisobutylenes with cyclodextrins

Designed Monomers and Polymers, 1998

Average Molecular Structure of Gasoline Engine Combustion Chamber Deposits Obtained by Solid-State 13 C, 31 P, and 1 H Nuclear Magnetic Resonance Spectroscopy

SAE Technical Paper Series, 1993

Journal of Food Research, 2014

SAE Technical Paper Series, 2010

A Review of Applications of NMR Spectroscopy in the Petroleum Industry

Spectroscopic Analysis of Petroleum Products and Lubricants, 2011

Relationship Between Combustion Chamber Deposits, Fuel Composition, and Combustion Chamber Deposit Structure

SAE Technical Paper Series, 1993

Environmental Science & Technology, 1996

Omega-3 fatty acid composition of samples taken from various points in a nutritional supplement manufacturing process. Excellent correlations were obtained on all 4 NMR instruments proving that NMR technology is applicable to in-lab, at-line. or on-line analysis of fish oil derived omega-3 fatty acid supplements. The 40 second NMR analysis effectively replaces a 60+ minute GC analysis.
Physical and chemical property determination of diesel fuels where excellent correlations were obtained between 1H NMR variability and parameters such as density, aromatic content by GC, hydrogen content by 1H TD-NMR (ASTM D7171 method), and sulfur content. Many more physical and chemical properties can be correlated to the 1H NMR spectrum allowing a single 40 second NMR experiment to predict 10-15 parameters that each require dedicated analyzers.
Finally, we will present the concept and initial results from an independent server-based NMR application software that can be utilized in conjunction with the NMR software of the current benchtop NMR systems, or alternatively as a stand-alone application platform. This software would effectively make chemometric and direct measurement NMR application ubiquitous across all NMR platforms.

Carbon, 2010

Macromolecules, 2003

Applied Catalysis A-general, 1999

Molecular composites: design of inclusion complexes of polyisobutylenes with cyclodextrins

Designed Monomers and Polymers, 1998

QNMR Cider Analysis CiderCon 2018 JCE

1H NMR Analysis of Cider - Apples - Fermentations - Juice - Aging - Spanish Cider - glycerol cons... more 1H NMR Analysis of Cider - Apples - Fermentations - Juice - Aging - Spanish Cider - glycerol consumption - complex chemical fingerprint for component quantification (ethanol, fusels, organic acids, sugars, amino acids, etc)

In the scope of analytical method validation it is generally accepted, in the arena outside of NM... more In the scope of analytical method validation it is generally accepted, in the arena outside of NMR spectroscopy, that validation should include inter-laboratory comparison (ILC) studies or proficiency testing coordinated by a relevant third-party organization such as AOAC, AOCS, ASTM, ISO, USP, etc. Validated NMR methods that are in general use by the industrial community under the auspices of official organizations are very limited. The reasons for the lack of official NMR methods is often stated to be due to the high cost of NMR instrumentation and the fact that it resides in research centers rather than in manufacturing plant laboratories. Over the years, chromatography has been preferred in these environments even though it requires constant calibration with expensive standards. As a primary method NMR does not require continued calibration with standards and appropriate utilization of superconducting and benchtop systems to provide ID and qNMR in purity, potency, and complex mixture analysis could greatly reduce the burden on chromatography approaches. A short review of the limited number of NMR-based inter-laboratory comparisons will be presented to provide a background to this topic. Further discussion will elaborate on the role that the ValidNMR organization could play as an interface between standard method development in industry and the requirement to determine intra-lab and inter-lab error and bias through ILC studies or third-party coordinated proficiency testing.

NMR Spectroscopy is the premier tool utilized by chemists to obtain detailed chemical information... more NMR Spectroscopy is the premier tool utilized by chemists to obtain detailed chemical information on molecular structure and is used extensively in molecular structure verification, chemical purity analysis, and complex mixture analysis. We have developed a quantitative NMR analysis that yields a chemical fingerprint that brewers can utilize to follow detailed variations in the chemistry observed in the various stages of the brewing process (malting, mashing, boiling, fermentation, ageing, and blending). The analysis observes all molecules in the beer at the same time and each molecular component (acids, alcohols, amino acids, malt-oligosaccharides) yields a unique spectral fingerprint pattern that is related to the structure of the molecule. Though the spectrum consists of a large number of overlapped individual fingerprints it is possible to identify and quantify individual components because many components have signals that appear at unique and specific points in the spectrum. The quantitative analysis is performed by comparing the area under the individual molecule signals to that of an internal standard (Maleic Acid 99%). Molecular components are quantified on a weight/volume basis in mg/L (parts-per million). Ethanol is also quantified on a %volume/volume basis.
The technique is not only applicable to the brewing process but is also being utilized to gain detailed chemical understanding of cider-making process, as well as the production of wine, mead, sake, spirits, and kombucha. Our laboratory has been developing this method with the help of a number of breweries following changes in batches of standard beers (Kolsch, Stout, Scots Ale, Barley Wine) as the brewing process is tweaked and changed over the course of 2 years. We have looked not just at finished beers but have studied dextrin solubility and chemistry of wort made from different malts, the effect of temperature on sour mashing, the effect of wild yeast and bacteria on various aspects of beer chemistry, as well as troubleshooting of “out of sensory target range” beers. The analysis requires very little sample preparation, has a large (orders of magnitude) linear concentration range of applicability and observes a large number of components in a single test that does not require constant re-calibration with expensive standards.

NMR Validation Workshop Presentation - PANIC 2016

Fruitex-B® (FrxB) is a patented plant mineral complex that is marketed as a nutritional supplemen... more Fruitex-B® (FrxB) is a patented plant mineral complex that is marketed as a nutritional supplement with potential health benefits for conditions linked to inflammation such as bone, joint and cardiovascular conditions. The original product was a calcium fructoborate complex formed by the reaction of boric acid with fructose and calcium carbonate. Recently a Magnesium salt version of the product has been produced and this study represents an investigation into the similarity between the calcium and magnesium salt versions of the product. Liquid and solid-state 13 C and 11 B NMR was utilized to establish a baseline for product quality and to establish a robust testing method for both identification and quantification of the mono-complex and di-complex present in the product, as well as free borate and free fructose that is present in the finished product. A quantitative 13 C NMR method was developed to quantify free fructose content in the complex. Finally, an NMR based product stability study was performed to monitor molecular level stability of the complex at temperature ranging from 35-70 o C with exposure lasting from 2-18 hours.

Different sugar borate esters (SBE) are found in fruits, vegetables, nuts and legunes and they ar... more Different sugar borate esters (SBE) are found in fruits, vegetables, nuts and legunes and they are naturally absorbed by animal cells. Fructose and glucose borate esters are most common SBEs. In food they serve as soluble borate with potential health beneficial effects. The samples used foor this study are magnesium and calcium sugarborate complexes formed by the reaction of boric acid with different sugars (fructose, glucose, galactose, mannose and sucrose) and magnesium or calcium carbonate. Liquid and solid-state 13 C and 11 B NMR was utilized to establish a baseline for product quality and to establish a robust testing method for both identification and quantification of the mono-complex and the di-complex present in the product, as well as free borate and free sugar that is present in the finished product. The effect of varying the salt form and the sugar component of the borate complex component was studied by 11 B and 13 C NMR to establish the relative amounts of free borate, free sugar, and mono-/di-complex present in the products formed by the manufacturing recipe changes.

Over the years much debate has centered around the validity and accuracy of NMR measurements to a... more 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 13 C 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" carbon structure present in the sample. Utilizing methodologies developed by Pugmire and Solum 1 for the solid-state 13 C NMR analysis of coals and other carbonaceous solids we have developed a liquid-state 13 C NMR methodology 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 13 C single pulse excitation which observes "all carbons in the observes only the protonated carbons in the sample. Though the DEPT-45 results are not quantitative across all carbon types (CH, CH 2 , and CH 3 ) due to polarization transfer differences, the technique is well enough understood that simple multiplication factors allow the relative absolute intensities of the different carbons to be determined. An additional aspect of the experiments is the addition of a standard material (Polyethyleneglycol (PEG) polymer) that allows the calculation of the absolute percentage of the carbons that are observed by the 13 C 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 2 . The ring sizes determined by this new combined NMR method are in agreement with FTICR-MS and fluorescence measurements 3-6 .

1 H NMR of a series of samples taken from different points in the manufacturing process of a fish... more 1 H NMR of a series of samples taken from different points in the manufacturing process of a fish oil nutritional supplement were obtained on a 300 MHz superconducting NMR system and a cryogen-free bench-top 60 MHz NMR system. The resulting spectra were utilized to develop single wide-range partial least-squares regression models of the EPA and DHA omega-3 fatty acid content of the fish oils at the various sampling points on the process. The process involves initial concentration of the fatty acids by solvent precipitation, molecular distillation, ethyl ester esterification, clathration, and centrifugation. For each of the fatty acids a single full range PLS model was obtained utilizing the entire integral binned/normalized spectrum or utilizing a series of normalized peak integrations rather than the entire spectrum. It was demonstrated that 60 MHz NMR spectra yielded identical model performance to the higher resolution 300 MHz spectra. The 60 MHz system is compact enough that it can be placed in the manufacturing plant environment for at-line utilization. Alternatively it can be packaged to provide on-line/in-line process control.

A compact high resolution NMR system will be described that can be situated on the bench-top or i... more 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 . The systems utilized since the early 1990's are capable of single channel operation on higher sensitivity nuclei ( 1 H, 19 F, 31 P, 23 Na, 7 Li, 11 B). A new generation of NMR systems are now being manufactured featuring multi-channel operation giving the possibility to monitor two nuclei at once or to perform 1H-13C-DEPT and higher sensitivity approaches to 13C observation. In pharmaceutical applications the Aspect-AI 60 MHz system was utilized in a reaction monitoring scenario where a reaction was monitored simultaneously on a split sample loop by the 60 MHz NMR and a 400 MHz Bruker Avance III superconducting NMR spectrometer [2]. The results obtained on the two systems were virtually identical indicating that the 60 MHz NMR system can be used to transfer PAT knowledge generated on pharmaceutical reactions in the research lab to the manufacturing areas for production monitoring.

Much debate has centered around the validity and accuracy of NMR measurements to accurately descr... more 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 13 C 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 13 C NMR analysis of coals and other carbonaceous solids [1], we have developed a new liquid-state 13 C NMR method that allows the relative quantification of overlapping protonated and bridgehead aromatic carbon signals to be determined [2].

Process NMR Associates LLC, 87A Sand Pit Rd, Danbury CT 06810 Nuclear magnetic resonance spectros... more Process NMR Associates LLC, 87A Sand Pit Rd, Danbury CT 06810 Nuclear magnetic resonance spectroscopy (NMR) was first developed in 1946 by research groups at Stanford and M.I.T., in the USA. The radar technology developed during World War II made many of the electronic aspects of the NMR spectrometer possible. With the newly developed hardware physicists and chemists began to apply the technology to chemistry and physics problems. Over the next 50 years NMR developed into the premier organic spectroscopy available to chemists to determine the detailed chemical structure of the chemicals they were synthesizing. Another well-known product of NMR technology has been the Magnetic Resonance Imager (MRI), which is utilized extensively in the medical radiology field to obtain image slices of soft tissues in the human body. In recent years, NMR has moved out of the research laboratory and into the on-line process analyzer market. This has been made possible by the production of stable permanent magnet technologies that allow high-resolution 1 H NMR spectra to be obtained in a process environment.

"Sulfuric Acid Alkylation Process Control" John Edwards, in Process/Industrial Instruments and Controls, 5th Ed., Eds. Gregory K. McMillan, Douglas M. Considine, McGraw-Hill, 1999

“A Review of Applications of NMR Spectroscopy in Petroleum Chemistry” John C. Edwards, Chapter 16 in Monograph 9 on Spectroscopic Analysis of Petroleum Products and Lubricants, Editor: Kishore Nadkarni, ASTM Books, 2011.

Process NMR Spectroscopy: Technology and On-line Applications” Chapter 10 in Process Analytical Technology: Spectroscopic Tools and Implementation Strategies for the Chemical and Pharmaceutical Industries, Blackwell-Wiley, 2010

Over the past few years our analytical NMR service has been developing a detailed chemical finger... more Over the past few years our analytical NMR service has been developing a detailed chemical fingerprint analysis of alcoholic beverages by quantitative 1 H NMR (qHNMR). Beyond the typical analyses of beer, wine, port, hard cider, sake and spirits, we have been looking at other fermented beverages such as kombucha, kefir, kvass, mead, alcoholic ginger beer, alcoholic root beer, and perry. As well as the final fermented beverage products, we have been actively investigating the various starting materials such as malt wort, apple juice, honey, grape juice, fruit juices, tea, and coffee. The NMR analysis can provide a rapid quantitative analysis without any sample preparation based on the molar ratio of integration value of unique molecular fingerprint peaks with the integrated signal of an internal standard. In our case we typically use maleic acid as an internal standard as it's singlet signal peak appears in a non-overlapping area of the spectrum compared to the chemistry we are interested in following. The information that can be derived from the NMR experiment covers a wide dynamic range of component molecule concentrations from 10-100,000 ppm. The analysis observes all fully dissolved chemical constituents and the spectral response is linear with regard to all chemical types. As a primary analytical method the chemist or brewer can utilize the well understood literature on the NMR chemical shifts and couplings that allow first principle analysis of each molecular fingerprint to identify and quantify the presence of targeted and non-targeted molecules in the complex mixture. The analysis provides quantitative information on the following chemical components: ethanol, higher (C3,C4,, maltose, 1,6-and 1,4-dextrin chemistry, maltotriose, lactose), polyphenols. It can also provide information on yeast metabolism products such as 2,3-butandiol (directly from Enterobacter activity or from the action of saccharomyces on diacetal which is a well-known beer flavor deviation), 1,3-propandiol (from yeast action on glycerol after carbohydrates have been entirely fermented from the beverage). In recent years kombucha has been found to contain more than 0.5% v/v ethanol. This fact could lead them to be classified as alcoholic beverages and bring the product under scrutiny and taxation by the Alcohol and Tobacco Tax and Trade Bureau which federally regulates the alcoholic beverage industry. Kombucha is a sweetened black or green tea that has been inoculated with a symbiotic culture of bacteria and yeast (SCOBY) which ferments in both the manufacturing process and in the bottle during the shipment and shelf life of the product. The drink is sold under the premise that the SCOBY, and the fermented drink, provide a probiotic culture to the consumer. In order to maintain an active probioic product the acitivity of the culture is not arrested by pasteurization or by addition of sorbate at the end of the fermentation stage. The kombucha is bottled with active SCOBY present in a sugar containing tea drink. Fermentation is then thought to occur during shipment, distribution and while the product sits on shelves leading to a final alcohol content greater than 0.5% ABV when the drink is purchased and consumed. We have utilized 1H NMR to obtain quantitative ethanol concentrations on a number of kombucha beverages bought off the shelf at grocery stores. The samples we analyzed represent the entire dataset of kombuchas that we purchased and they represent the products of 5 different manufacturers. We also aged two of the products at room temperature for 7 months and analyzed them to observe the effect of long term aging on kombucha products. We also quantitatively analyzed the sample for various organic acid concentrations as well as residual sugars. Experimental: 1H NMR spectra were acquired on a Varian Mercury-300MVX spectrometer operating at a resonance frequency of 299.67 MHz and equipped with a Varian 5mm ATB PFG probe.

In recent years quantitative nuclear magnetic resonance spectroscopy (qNMR) has become a premier ... more In recent years quantitative nuclear magnetic resonance spectroscopy (qNMR) has become a premier tool for purity analysis of drugs and pharmaceuticals and the long-term link of NMR with metabolomics has also driven the application of qNMR to complex mixtures. 1H NMR is ideal for rapid analysis of complex mixture samples with minimal sample preparation by the addition of a known quantity of internal standard (typically a small molecule such as maleic acid with a single peak in a non-overlapping area of the spectrum) which then allows direct molar ratios to be established between the standard and dozens of chemical components in a mixture such as beer, wine, cider, kombucha, sake and hard seltzers. qNMR is acknowledged as a primary method for the identification of molecules and, under the correct conditions, is quantitative across a large dynamic range with a uniform response for all protons observed in the sample regardless of molecular chemistry. qNMR analysis is a molar balance that allows all components to be observed directly and quantitatively in a 5-10 minute experiment allowing the quantification of alcohols (ethanol, methanol, fusel alcohols, glycerol), organic acids (acetic, lactic, malic, succinic, formic, tartaric), carbohydrates (sucrose, glucose, lactose, fructose, maltose, residual branched dextrins), amino acids, and yeast and bacterial metabolites of fermentation (2,3-butandiol, 1-3-propandiol), esters, chemistry from additions (caffeine from coffee, quinic acid from cranberries, preservatives such as sorbate and benzoate, etc.). The chemical components can be summed to provide a calorie value as well as nutritional label information. The chemistry of the beverages can be observed at any point in the fermentation process from starting brewers mash or fruit juice to different points in the fermentation and then at various stages of ageing. We have used the technique to define finished products and the reproducibility of a fermentation process. To identify the action of additional fermentation processes such as glycerol fermentation in “dry” fermentations such as Barrel-Aged Spanish cider or Barrel-Aged sour beers. The window into the complex chemistry of these products allows targeted and non-targeted approaches to identify batch to batch differences that explain off-flavors, exploding cans and bottles, unexpected attenuation problems, product haze, non-conformity to ethanol concentrations (high and low). The technique is applicable to non-alcoholic beverages such as energy drinks, soda, aloe vera drinks, fruit juices, tea and coffee along with side-products such as vinegars, distilled spirits, honey, maple syrup.