Computer Assisted Structure Elucidation (CASE): Current and future perspectives.

The first efforts for the development of methods for Computer-Assisted Structure Elucidation (CASE) were published more than 50 years ago. CASE expert systems based on one-dimensional (1D) and two-dimensional (2D) Nuclear Magnetic Resonance (NMR) data have matured considerably by now. The structures of a great number of complex natural products have been elucidated and/or revised using such programs. In this article, we discuss the most likely directions in which CASE will evolve. We act on the premise that a synergistic interaction exists between CASE, new NMR experiments, and methods of computational chemistry, which are continuously being improved. The new developments in NMR experiments (long-range correlation experiments, pure-shift methods, coupling constants measurement and prediction, residual dipolar couplings [RDCs]), and residual chemical shift anisotropies [RCSAs], evolution of density functional theory (DFT), and machine learning algorithms will have an influence on CASE systems and vice versa. This is true also for new techniques for chemical analysis (Atomic Force Microscopy [AFM], "crystalline sponge" X-ray analysis, and micro-Electron Diffraction [micro-ED]), which will be used in combination with expert systems. We foresee that CASE will be utilized widely and become a routine tool for NMR spectroscopists and analysts in academic and industrial laboratories. We believe that the "golden age" of CASE is still in the future.

NMReDATA, a standard to report the NMR assignment and parameters of organic compounds.

Even though NMR has found countless applications in the field of small molecule characterization, there is no standard file format available for the NMR data relevant to structure characterization of small molecules. A new format is therefore introduced to associate the NMR parameters extracted from 1D and 2D spectra of organic compounds to the proposed chemical structure. These NMR parameters, which we shall call NMReDATA (for nuclear magnetic resonance extracted data), include chemical shift values, signal integrals, intensities, multiplicities, scalar coupling constants, lists of 2D correlations, relaxation times, and diffusion rates. The file format is an extension of the existing Structure Data Format, which is compatible with the commonly used MOL format. The association of an NMReDATA file with the raw and spectral data from which it originates constitutes an NMR record. This format is easily readable by humans and computers and provides a simple and efficient way for disseminating results of structural chemistry investigations, allowing automatic verification of published results, and for assisting the constitution of highly needed open-source structural databases.

Wood Extractives Promote Cellulase Activity on Cellulosic Substrates.

Deposition of hydrophobic wood extractives and representative model compounds, on the surface of cellulose prior to enzymatic hydrolysis was found to either enhance or inhibit the action of cellulase enzymes. The effect of these compounds was correlated with their chemical structure, which may in part explain the differential effects observed between softwood and hardwood extractives. Specifically, the addition of sterol, enhanced enzymatic hydrolysis of microcrystalline cellulose by 54%, whereas the addition of a triglyceride could inhibit the hydrolysis by 49%. The effects of the different extractives' could be explained by considering their Hansen solubility parameters. The amphiphilic and/or hydrophobic character of model extractives was found to be the variable that affected the deposition of extractives on cellulose surfaces and the eventual adsorption of cellulolytic enzymes on it. The observed beneficial effects of extractives are likely related to a reduction in the irreversible binding of the enzymes on the cellulose surface.

Synthesis, Characterization, and Antimicrobial Efficacy of Photomicrobicidal Cellulose Paper.

Toward our goal of scalable, antimicrobial materials based on photodynamic inactivation, paper sheets comprised of photosensitizer-conjugated cellulose fibers were prepared using porphyrin and BODIPY photosensitizers, and characterized by spectroscopic (infrared, UV-vis diffuse reflectance, inductively coupled plasma optical emission) and physical (gel permeation chromatography, elemental, and thermal gravimetric analyses) methods. Antibacterial efficacy was evaluated against Staphylococcus aureus (ATCC-2913), vancomycin-resistant Enterococcus faecium (ATCC-2320), Acinetobacter baumannii (ATCC-19606), Pseudomonas aeruginosa (ATCC-9027), and Klebsiella pneumoniae (ATCC-2146). Our best results were achieved with a cationic porphyrin-paper conjugate, Por((+))-paper, with inactivation upon illumination (30 min, 65 ± 5 mW/cm(2), 400-700 nm) of all bacterial strains studied by 99.99+% (4 log units), regardless of taxonomic classification. Por((+))-paper also inactivated dengue-1 virus (>99.995%), influenza A (∼ 99.5%), and human adenovirus-5 (∼ 99%). These results demonstrate the potential of cellulose materials to serve as scalable scaffolds for anti-infective or self-sterilizing materials against both bacteria and viruses when employing a photodynamic inactivation mode of action.

Kraft lignin chain extension chemistry via propargylation, oxidative coupling, and Claisen rearrangement.

Despite its aromatic and polymeric nature, the heterogeneous, stochastic, and reactive characteristics of softwood kraft lignin seriously limit its potential for thermoplastic applications. Our continuing efforts toward creating thermoplastic lignin polymers are now focused at exploring propargylation derivatization chemistry and its potential as a versatile novel route for the eventual utilization of technical lignins with a significant amount of molecular control. To do this, we initially report the systematic propargylation of softwood kraft lignin. The synthesized derivatives were extensively characterized with thermal methods (DSC, TGA), (1)H, (13)C, and quantitative (31)P NMR and IR spectroscopies. Further on, we explore the versatile nature of the lignin pendant propargyl groups by demonstrating two distinct chain extension chemistries; the solution-based, copper-mediated, oxidative coupling and the thermally induced, solid-state, Claissen rearrangement polymerization chemistries. Overall, we show that it is possible to modulate the reactivity of softwood kraft lignin via a combination of methylation and chain extension providing a rational means for the creation of higher molecular weight polymers with the potential for thermoplastic materials and carbon fibers with the desired control of structure-property relations.

Efficient one-pot synthesis of 5-chloromethylfurfural (CMF) from carbohydrates in mild biphasic systems.

5-Halomethylfurfurals can be considered as platform chemicals of high reactivity making them useful for the preparation of a variety of important compounds. In this study, a one-pot route for the conversion of carbohydrates into 5-chloromethylfurfural (CMF) in a simple and efficient (HCl-H3PO4/CHCl3) biphasic system has been investigated. Monosaccharides such as D-fructose, D-glucose and sorbose, disaccharides such as sucrose and cellobiose and polysaccharides such as cellulose were successfully converted into CMF in satisfactory yields under mild conditions. Our data shows that when using D-fructose the optimum yield of CMF was about 47%. This understanding allowed us to extent our work to biomaterials, such as wood powder and wood pulps with yields of CMF obtained being comparable to those seen with some of the enumerated mono and disaccharides. Overall, the proposed (HCl-H3PO4/CHCl3) optimized biphasic system provides a simple, mild, and cost-effective means to prepare CMF from renewable resources.

Novel and Integrated Process for the Valorization of Kraft Lignin to Produce Lignin-Containing Vitrimers.

The valorization of lignin into value-added products by oxidative conversion is a widely studied strategy. However, in many cases, this approach has limited scope for integration into industrial processes. The objective of our work is to maximize overall lignin utilization to produce diverse value-added products with a focus on integration in the existing industrial pulp and paper processes. The utilization of the sequential oxidation strategy using oxygen and ozone resulted in kraft lignin with a marked improvement in carboxyl content and also allowed the formation of vanillin and vanillic acid in the oxygen stage. The sequentially oxidized lignin (OxL-COOH) was then cured with poly(ethylene glycol) diglycidyl ether (PEG-epoxy) to form high-lignin-content (>48 wt %) vitrimers with high thermal stability, fast relaxation, swelling, and self-healing due to the presence of bond-exchangeable cross-linked networks. Overall, this study provides a novel approach for the multidimensional valorization of lignin and demonstrates an integrated approach for kraft lignin valorization in the pulp and paper industry.

Kraft Lignin: A Valuable, Sustainable Resource, Opportunities and Challenges.

Kraft lignin, a by-product from the production of pulp, is currently incinerated in the recovery boiler during the chemical recovery cycle, generating valuable bioenergy and recycling inorganic chemicals to the pulping process operation. Removing lignin from the black liquor or its gasification lowers the recovery boiler load enabling increased pulp production. During the past ten years, lignin separation technologies have emerged and the interest of the research community to valorize this underutilized resource has been invigorated. The aim of this Review is to give (1) a dedicated overview of the kraft process with a focus on the lignin, (2) an overview of applications that are being developed, and (3) a techno-economic and life cycle asseeements of value chains from black liquor to different products. Overall, it is anticipated that this effort will inspire further work for developing and using kraft lignin as a commodity raw material for new applications undeniably promoting pivotal global sustainability concerns.

Copolymers of starch, a sustainable template for biomedical applications: A review.

The outstanding versatility of starch offers a source of inspiration for the development of high-performance-value-added biomaterials for the biomedical field, including drug delivery, tissue engineering and diagnostic imaging. This is because starch-based materials can be tailored to specific applications via facile grafting or other chemistries, introducing specific substituents, with starch being effectively the "template" used in all the chemical transformations discussed in this review. A considerable effort has been carried out to obtain specific tailored starch-based grafted polymers, taking advantage of its biocompatibility and biodegradability with appealing sustainability considerations. The aim of this review is to critically explore the latest research that use grafting chemistries on starch for the synthesis of products for biomedical applications. An effort is made in reviewing the literature that proposes synthetic "greener" approaches, the use of enzymes and their immobilized analogues and alternative solvent systems, including water emulsions, ionic liquids and supercritical CO2.

Photobactericidal porphyrin-cellulose nanocrystals: synthesis, characterization, and antimicrobial properties.

Adherence and survival of pathogenic bacteria on surfaces leading to concomitant transmission to new hosts significantly contributes to the proliferation of pathogens, which in turn considerably increases the threat to human health, particularly by antibiotic-resistant bacteria. Consequently, more research into effective surface disinfection and alternative materials (fabrics, plastics, or coatings) with antimicrobial and other bioactive characteristics is desirable. This report describes the synthesis and characterization of cellulose nanocrystals that were surface-modified with a cationic porphyrin. The porphyrin was appended onto the cellulose surface via the Cu(I)-catalyzed Huisgen-Meldal-Sharpless 1,3-dipolar cycloaddition having occurred between azide groups on the cellulosic surface and porphyrinic alkynes. The resulting, generally insoluble, crystalline material, CNC-Por (5), was characterized by infrared and diffusion (1)H NMR spectroscopies, gel permeation chromatography, and thermogravimetric analysis. Although only suspended, and not dissolved, in an aqueous system, CNC-Por (5) showed excellent efficacy toward the photodynamic inactivation of Mycobacterium smegmatis and Staphylococcus aureus , albeit only slight activity against Escherichia coli . The synthesis, properties, and activity of CNC-Por (5) described herein serve as a benchmark toward our overall objectives of developing novel, potent, bioactive, photobactericidal materials that are effective against a range of bacteria, with potential utilization in the health care and food preparation industries.

Understanding the radical mechanism of lipoxygenases using 31P NMR spin trapping.

In this paper, we use our quantitative (31)P NMR spin trapping methods, already developed for simple oxygen- and carbon-centered radicals, to understand the radical intermediates generated by enzymatic systems and more specifically lipoxygenases. Our methodology rests on the fact that free radicals react with the nitroxide phosphorus compound, 5-diisopropoxy-phosphoryl-5-methyl-1-pyrroline-N-oxide (DIPPMPO), to form stable radical adducts, which are suitably detected and accurately quantified using (31)P NMR in the presence of a phosphorus containing internal standard. This system was thus applied to better understand the mechanism of enzymatic oxidation of linoleic acid by soybean lipoxygenases-1 (LOX). The total amount of radicals trapped by DIPPMPO was detected by (31)P NMR at different experimental conditions. In particular the effect of dioxygen concentration on the amount of radicals being trapped was studied. At low dioxygen concentration, a huge increase of radicals trapped was observed with respect to the amount of radicals being trapped at normal dioxygen concentrations.

Quantitative 31P NMR Analysis of Lignins and Tannins.

The development of sustainable biorefinery products is confronted, among others, with the challenge of lignin and tannin valorization. These abundant, renewable aromatic biopolymers have not been widely exploited due to their inherent structural complexity and high degrees of variability and species diversity. The lack of a defined primary structure for these polyphenols is further compounded with complex chemical alterations induced during processing, eventually imparting a large variety of structural features of extreme significance for any further utilization efforts. Consequently, a protocol for the rapid, simple, and unequivocal identification and quantification of the various functional groups present in natural polyphenols, is a fundamental prerequisite for understanding and accordingly tailor their reactivity and eventual utility. Quantitative 31P NMR offers the opportunity to rapidly and reliably identify unsubstituted, o-mono substituted, and o-disubstituted phenols, aliphatic OHs, and carboxylic acid moieties in lignins and tannins with broad application potential. The methodology consists of an in situ quantitative lignin or tannin labeling procedure using a suitable 31P containing probe, followed by the acquisition of a quantitative 31P NMR spectrum in the presence of an internal standard. The high natural abundance of the 31P nucleus allows for small amounts of the sample (~30 mg) and short NMR acquisition times (~30-120 min) with well-resolved 31P signals that are highly dependent on the surrounding chemical environment of the labeled OH groups.

Regular linking of cellulose nanocrystals via click chemistry: synthesis and formation of cellulose nanoplatelet gels.

Over a number of years work in our laboratory has been developing new chemistry for the use of cellulose nanocrystals (CNCs) as scaffolds for the creation of nanomaterials with novel, stimuli responsive characteristics. Our work takes advantage of the rigid nature of CNCs, the unique nanopattern etched on their surface in the form of regularly spaced primary OH groups, and the fact that these materials have all reducing end groups located on one end. In this communication, a method for the grafting of amine-terminated monomers onto surface-modified CNCs followed by click chemistry is demonstrated. Initially the primary hydroxyl groups on the surface of the CNCs were selectively activated by converting them to carboxylic acids by the use of TEMPO-mediated hypohalite oxidation. Further reactions using the activated TEMPO-oxidized CNCs were carried out via carbodiimide-mediated formation of an amide linkage between precursors carrying an amine functionality and the carboxylic acid groups on the surface of the TEMPO-oxidized CNCs. Subsequently, two sets of CNCs were prepared, containing on their surface an azide derivative and an alkyne derivative, respectively. Finally, the click chemistry reaction, that is, the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition between the azide and the alkyne, surface-activated CNC was employed, bringing together the nanocrystalline materials in a unique regularly packed arrangement demonstrating a degree of molecular control for creating these structures at the nano level.

Characterization of free radical spin adducts of the DIPPMPO using mass spectrometry and (31)P NMR.

5-Diisopropyloxy-phosphoryl-5-methyl-1-pyrroline-N-oxide (DIPPMPO) was used to trap a variety of free radicals and the stable compounds generated by the natural decomposition of the initially formed spin adducts were characterized by (31)P nuclear magnetic resonance (NMR) and mass spectrometry. Initially, the starting spin trap DIPPMPO was completely characterized using GC-MS and its fragmentation pathway was studied in detail. Then, DIPPMPO was used to trap an oxygen-centered free radical (the hydroxyl radical *OH) and two carbon- centered free radicals (methyl *CH(3) and 1-phenyl-ethanol-1-yl *CCH(3)(OH)Ph radicals). The (31)P NMR signals were thus assigned and the structures of adducts were studied and confirmed by mass spectrometry. Overall, the fragmentation pathways of the radical adducts proceed mainly via the loss of the diisopropyloxy(oxido)phosphoranyl radical. For the specific case of trapping *OH radicals, it is possible to visualize the rearrangement of the nitroxide radical adduct to its nitrone form as invoked in the literature. This spin trapping technique, coupled with (31)P NMR and MS, provides a tool for the identification of short-lived and low molecular weight free radicals present in a variety of processes.

3D Photoinduced Spatiotemporal Resolution of Cellulose-Based Hydrogels for Fabrication of Biomedical Devices.

Rational spatiotemporal irradiation of cellulose-based hydrogels (carboxymethylcellulose (CMC), citric acid, and riboflavin) using a laser diode stereolithography 3D printer obtained architectures referred to as photodegradation addressable hydrogels (PAHs). Under irradiation, these PAHs engage in an unprecedented spatially resolved zonal swelling illustrating marked but controllable changes in swelling and thickness while concomitantly obtaining improved oxygen transmission rate values by 5 times. XPS, carboxyl content, and swelling data comparisons of hydrogel formulations show that photodegradation and ablation of the material occur, where hydroxyl sites of CMC are converted to aldehydes and ketones. XRD data show that the total number of crystalline aggregates in the material are lowered after photoablation. The spatially tuned (photoablated) hydrogel films can thus be shaped into a lens form. The energy required for the lens tuning process can be lowered up to 30 times by incorporation of riboflavin in the films. The method demonstrated here enables the processing of a material that is difficult to be machined or cast by popular contact lens making methods.

Chlorines Are Not Evenly Substituted in Chlorinated Paraffins: A Predicted NMR Pattern Matching Framework for Isomeric Discrimination in Complex Contaminant Mixtures.

Chlorinated paraffins (CPs) can be mixtures of nearly a half-million possible isomers. Despite the extensive use of CPs, their isomer composition and effects on the environment remain poorly understood. Here, we reveal the isomeric distributions of nine CP mixtures with single-chain lengths (C14/15) and varying degrees of chlorination. The molar distribution of C n H2n+2-m Cl m in each mixture was determined using high-resolution mass spectrometry (MS). Next, the mixtures were analyzed by applying both one-dimensional 1H, 13C and two-dimensional nuclear magnetic resonance (NMR) spectroscopy. Due to substantially overlapping signals in the experimental NMR spectra, direct assignment of individual isomers was not possible. As such, a new NMR spectral matching approach that used massive NMR databases predicted by a neural network algorithm to provide the top 100 most likely structural matches was developed. The top 100 isomers appear to be an adequate representation of the overall mixture. Their modeled physicochemical and toxicity parameters agree with previous experimental results. Chlorines are not evenly distributed in any of the CP mixtures and show a general preference at the third carbon. The approach described here can play a key role in understanding of complex isomeric mixtures such as CPs that cannot be resolved by MS alone.