Designing effective and selective reactions at sustainable or mild conditions is key for the valorization or refinery of lignin biomass using H2 reduction methods. However, it remains unclear what are the feasible mildest conditions for the reductive valorization of lignin, at which transformations can be designed. Here, we aim to exploit this critically important question using quantum chemistry calculations to systematically analyze the thermodynamics of hydrogenation and hydrogenolysis of typical functional groups found in lignin based on a set of aromatic model compounds. Our results show that it is thermodynamically feasible to break ether linkages and remove oxygen content in the model compounds even at room temperature, room pressure, and in aqueous solvent (i.e., the global mildest conditions). Interestingly, the potential influence on the thermodynamics by reaction variables is ranked in the order of temperature > H2 pressure > solvent dielectric constant; a strategically chosen solvent may enable increased selectivity for hydrogenolysis over hydrogenation. Our predicted reaction thermodynamics is consistent with our experimental findings of probed reaction pathways. This work may inspire researchers to pursue the design of “ultimate” green biomass conversion processes closer to the global mildest conditions.Keywords: Biomass; Gibbs free energy; Hydrogenation; Hydrogenolysis; Lignin;

Electrocatalytic upgrading of glycerol to value-added commodity is demonstrated using an ultralow loading of a cobalt-based oxidation catalyst at 16 μg cm−2. Reactions take place under ambient conditions in an aqueous environment, while generating H2 as a byproduct. Selectivity towards two major products, lactic acid and glyceric acid, can be controlled via simple variation of reaction conditions. The system is scalable and functions well even in the presence of methanol, an impurity commonly found in the industrial bio-diesel waste stream. Industrial glycerol waste from a local bio-diesel plant was also shown to be upgradable after a simple aqueous pretreatment.

Lignin represents a considerable source of renewable and bio-based carbon. Pulping processes enable lignin, together with all components of the lignocellulosic biomass, to enter valorizable streams. A current key objective is to further valorize this versatile aromatic biopolymer, and for that, to go beyond its mere energy use. Despite the emergence of numerous proposals for value-added products coming from lignin, most of them remain at the research stage. The main challenges arise from the complexity and heterogeneity of the lignin structure and resulting molecular properties, the variability of the biomass source, pre-treatment processes, and the growing environment. Keeping in mind that future integrated biorefineries must take into account environmental concerns, lignin processing in accordance with green chemistry principles should first be favoured. From this very perspective, this work proposes to review the most promising current routes towards fractionation and/or depolymerization of lignin. Those should represent sustainable treatment technologies potentially leading to a broad spectrum of marketable lignin-based molecules and products. First, lignin fractionation by selective precipitation using pH as well as green solvents, or by using membrane technologies, will be addressed. Then lignin depolymerization will be discussed at length, notably from a catalytic point of view and by hydrogenolysis; the knowledge about the fundamental chemistry stemming from the use of model compounds will be described. Substitution of organic solvents with environmentally harmless supercritical fluids or with negligible vapour pressure ionic liquids is of great interest to modify lignin, and is finally reviewed. Lastly, challenges for integrated biorefineries and for launching new lignin-based compounds and products will be discussed.

A copper-doped porous metal oxide catalyst in combination with hydrogen shows selective and quantitative hydrogenolysis of benzyl ketones and aldehydes, and hydrogenation of alkenes. The approach provides an alternative to noble-metal catalysed reductions and stoichiometric Wolff-Kishner and Clemmensen methods.

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In silico toxicity models are critical in addressing experimental aquatic toxicity data gaps and prioritizing chemicals for further assessment. Currently, a number of predictive in silico models for aquatic toxicity are available, but most models are challenged to produce accurate predictions across a wide variety of functional chemical classes. Appropriate model selection must be informed by the models’ applicability domain and performance within the chemical space of interest. Herein we assess five predictive models for acute aquatic toxicity to fish (ADMET Predictor™, Computer-Aided Discovery and REdesign for Aquatic Toxicity (CADRE-AT), Ecological Structure Activity Relationships (ECOSAR) v1.11, KAshinhou Tool for Ecotoxicity (KATE) on PAS 2011, and Toxicity Estimation Software Tool (TEST) v.4). The test data set was carefully constructed to include 83 structurally diverse chemicals distinct from the training data sets of the assessed models. The acute aquatic toxicity models that rely on properties related to chemicals’ bioavailability or reactivity performed better than purely statistical algorithms trained on large sets of chemical properties and structural descriptors. Most models showed a marked decrease in performance when assessing insoluble and ionized chemicals. In addition to comparing tool accuracy and, this analysis provides insights that can guide selection of modeling tools for specific chemical classes and help inform future model development for improved accuracy.

Toxicity is a concern with many chemicals currently in commerce, and with new chemicals that are introduced each year. The standard approach to testing chemicals is to run studies in laboratory animals (e.g. rats, mice, dogs), but because of the expense of these studies and concerns for animal welfare, few chemicals besides pharmaceuticals and pesticides are fully tested. Over the last decade there have been significant developments in the field of computational toxicology which combines in vitro tests and computational models. The ultimate goal of this field is to test all chemicals in a rapid, cost effective manner with minimal use of animals. One of the simplest measures of toxicity is provided by high-throughput in vitro cytotoxicity assays, which measure the concentration of a chemical that kills particular types of cells. Chemicals that are cytotoxic at low concentrations tend to be more toxic to animals than chemicals that are less cytotoxic. We employed molecular characteristics derived from density functional theory (DFT) and predicted values of log(octanol–water partition coefficient) (logP) to construct a design variable space, and built a predictive model for cytotoxicity based on U.S. EPA Toxicity ForeCaster (ToxCast) data tested up to 100 μM using a Näive Bayesian algorithm. External evaluation showed that the area under the curve (AUC) for the receiver operating characteristic (ROC) of the model to be 0.81. Using this model, we provide probabilistic design rules to help synthetic chemists minimize the chance that a newly synthesized chemical will be cytotoxic.

Synthetic chemicals and materials are the basis of our society and our economy. Yet, in spite of all the advances in toxicology that have helped us understand and even predict toxicity associated with industrial chemicals, fundamental scientific questions crucial to the development of safer chemicals are left unanswered. Alternative strategies, such as in silico toxicity predictions, are considered the next frontier in molecular design for reduced hazard; however, such strategies are still not sufficiently developed to meet existing needs. Design strategies need to incorporate information and data at the nexus of multiple disciplines. Critically, there is a need for the incorporation of toxicology into the design phase of the molecular design process. In this Feature, we discuss the current status and future challenges in molecular design for reduced hazard.Keywords: Building blocks; Design rules; Eco-innovation; Green toxicology; Life cycle assessment; MoDRN; Molecular design; NSMDS; Preventative toxicology; Principles of Green Chemistry; Property-based guidelines; Reduced hazard; Sustainability; Sustainable innovation; Synthesis; Systems thinking; Tox21; ToxCast; Toxicology

An increasingly important chemical transformation that will be necessary as we move toward sustainable manufacturing is the oxidation of C–H bonds. Our reported robust heterogeneous cobalt water oxidation catalyst, formed from a metal carbonyl phosphine complex as precursor, is now shown to be active for the selective oxidation of C–H bonds. Of 10 oxidants tested, only Oxone and its oxidatively active component KHSO5 proved competent. A wide variety of substrates were effectively oxidized with KHSO5, including heterocycles, alkyl arenes, alcohols, alkenes, and alkanes. The catalyst is highly selective for C–H bonds over water oxidation when the reaction is conducted in aqueous media. The catalyst can be recycled with minimal loss of activity while under N2. Preliminary mechanistic data are also discussed.

The Twelve Principles of Green Chemistry were first published in 1998 and provide a framework that has been adopted not only by chemists, but also by design practitioners and decision-makers (e.g., materials scientists and regulators). The development of the Principles was initially motivated by the need to address decades of unintended environmental pollution and human health impacts from the production and use of hazardous chemicals. Yet, for over a decade now, the Principles have been applied to the synthesis and production of engineered nanomaterials (ENMs) and the products they enable. While the combined efforts of the global scientific community have led to promising advances in the field of nanotechnology, there remain significant research gaps and the opportunity to leverage the potential global economic, societal and environmental benefits of ENMs safely and sustainably. As such, this tutorial review benchmarks the successes to date and identifies critical research gaps to be considered as future opportunities for the community to address. A sustainable material design framework is proposed that emphasizes the importance of establishing structure–property–function (SPF) and structure–property–hazard (SPH) relationships to guide the rational design of ENMs. The goal is to achieve or exceed the functional performance of current materials and the technologies they enable, while minimizing inherent hazard to avoid risk to human health and the environment at all stages of the life cycle.

We report a heterogeneous cobalt–phosphine-based water oxidation catalyst that was produced by thermal synthesis, and can be easily and rapidly deposited onto a variety of substrates from a suspension. Application of the catalyst dramatically improved the oxygen evolution efficiency and corrosion-resistance of stainless steel, nickel and copper anodes in alkaline media. More than 20 g of catalyst was prepared in a single batch, and it was shown to be effective at surface loadings as low as 20 μg/cm2. The catalyst was investigated in three different systems: (1) An alkaline electrolyzer with stainless steel electrodes activated with the catalyst supported 120–200% of the current density of an unactivated but otherwise identical electrolyzer, over a range of applied potentials, and maintained this improved efficiency throughout 1495 h of continuous use in 1 M NaOH. (2) Copper anodes were activated and protected from corrosion in dilute sodium hydroxide for 8 h of electrolysis, before a steady decrease in performance over the next 48 h. (3) Activation of nickel anodes with the catalyst reduced the required overpotential by 90–130 mV at current densities between 7.5 and 15 mA/cm2, thereby increasing the cell efficiency of water splitting as well as zinc deposition from alkaline zincate electrolytes. The cell efficiency for zinc deposition at a current density of 12.5 mA/cm2 was improved from 68.0% with a nickel anode to 72.0% with 50 μg/cm2 catalyst on the nickel anode.Keywords: Cobalt oxide; Copper anode; Electrocatalyst; Electrolysis; Energy storage; Green chemistry; Heterogeneous catalyst; Water oxidation; Water splitting; Zinc electrowinning; Zinc−air fuel cell;

Isolated, solvent-extracted lignin from candlenut (Aleurites moluccana) biomass was subjected to catalytic depolymerization in methanol with an added pressure of H2, using a porous metal oxide catalyst (PMO) derived from a Cu-doped hydrotalcite-like precursor. The Cu-PMO was effective in converting low-molecular weight lignin into simple mixtures of aromatic products in high yield, without char formation. Gel permeation chromatography was used to track changes in molecular weight as a result of the catalytic treatments and product mixtures were characterized by 1H and 13C NMR spectroscopy. In the temperature range 140–220 °C, unusual C9 catechols were obtained with high selectivity. Lignin conversion of >90% and recovery of methanol-soluble products in yields of was >70% was seen at 180 °C with optimized catalyst and biomass loadings. At 140 °C, 4-(3-hydroxypropyl)-catechol was the major product and could be isolated in high purity.

We report the thermal synthesis of a heterogeneous Co–phosphine-based water oxidation catalyst that can be easily coated onto a variety of substrates. The system is active in neutral water and performs best with borate as electrolyte, in which the onset of catalytic current occurs at 1.51 V vs. RHE, with a Tafel slope of 68 mV per decade. Stable water oxidation is observed for over 40 hours; including in seawater with borate electrolyte, in which the catalyst is selective for water oxidation over chloride (85% Faradaic efficiency). The organic portion of the catalyst appears to play a crucial role in catalytic activity.

A mechanochemical oxidation of methoxylated aromatic chemicals is described, providing an example of a very different selectivity as compared to solution-based chemistry. Oxone was shown to react with 1,2,3-trimethoxybenzene to yield predominantly 2,6-dimethoxybenzoquinone in the solid state or 2,3,4-trimethoxyphenol in solution. The difference in effective acidity of the reaction conditions was not apparently responsible for the observed selectivity. The mechanochemical method described is simple, reproducible, and gave higher yield at higher conversion of substrate compared to solution conditions.

The mutagenic and carcinogenic effects of strong alkylating agents, such as epoxides, have been attributed to their ability to covalently bind DNA in vivo. Most olefins are readily oxidized to reactive epoxides by CytP450. In an effort to develop predictive models for olefin and epoxide mutagenicity, the ring openings of 15 halogen-, alkyl-, alkenyl-, and aryl-substituted epoxides were modeled by quantum-mechanical transition state calculations using MP2/6-31+G(d,p) in the gas phase and in aqueous solution. Free energies of activation (ΔG⧧) and free energies of reaction (ΔGrxn) were computed for each epoxide in the series. This study finds that an aqueous solution ΔGrxn threshold value of approximately −14.7 kcal/mol can be used to discern mutagenic/carcinogenic epoxides (ΔGrxn < −14.7 kcal/mol) from nonmutagens/noncarcinogens (ΔGrxn > −14.7 kcal/mol). The computed reaction thermodynamics are appropriate regardless of ring-opening mechanism in vivo and are thus proposed as an effective in silico screen and design guideline for decreasing potential mutagenicity and carcinogenicity of olefins and their respective epoxides.

Green Chemistry is a relatively new emerging field that strives to work at the molecular level to achieve sustainability. The field has received widespread interest in the past decade due to its ability to harness chemical innovation to meet environmental and economic goals simultaneously. Green Chemistry has a framework of a cohesive set of Twelve Principles, which have been systematically surveyed in this critical review. This article covers the concepts of design and the scientific philosophy of Green Chemistry with a set of illustrative examples. Future trends in Green Chemistry are discussed with the challenge of using the Principles as a cohesive design system (93 references).

Material and energy inefficiencies in total synthesis can arise from a lack of step economy. Multicomponent syntheses have the potential to optimize step economy and, in turn, to minimize not only waste, but also exposure to hazardous chemicals. Therefore, multicomponent syntheses are of immense interest to the field of Green Chemistry. Herein is described a multicomponent synthesis of arylnaphthalene lignan lactones, which are valuable natural products with promising anticancer and antiviral properties. In an effort to improve our previously reported one-pot, multicomponent synthesis an approach using phenylacetylene, phenylpropargyl chloride, carbon dioxide, catalytic silver iodide, and catalytic 18-crown-6 ether was developed. This methodology was then successfully applied to the preparation of dehydrodimethylconidendrin and its regioisomer, dehydrodimethylretroconidendrin.

Naturally occurring arylnaphthalene lactone lignans have demonstrated a variety of valuable medicinal chemistry properties and have therefore been of continued interest to drug discovery research. Our group has demonstrated a silver-catalyzed one-pot synthesis of the arylnaphthalene lactone core using carbon dioxide, phenylpropargyl chloride, and phenylacetylene. This new approach has been employed in the synthesis of six arylnaphthalene lactone natural products: retrochinensin (1), justicidin B (2), retrojusticidin B (3), chinensin (4), justicidin E (5), and taiwanin C (6). Additionally, an arylnaphthalene lactone regioisomer was isolated (9), which we refer to as isoretrojusticidin B.

In this review we will highlight some of the science that exemplifies the principles of Green Chemistry, in particular the efficient use of materials and energy, development of renewable resources, and design for reduced hazard. Examples are drawn from a diverse range of research fields including catalysis, alternative solvents, analytical chemistry, polymer science, and toxicology. While it is impossible for us to be comprehensive, as the worldwide proliferation of Green Chemistry research, industrial application, conferences, networks, and journals has led to a wealth of innovation, the review will attempt to illustrate how progress has been made toward solving the sustainability goals of the 21st century by engaging at the molecular level.

•Lignins structure is linked to the oil composition obtained after hydroprocessing.•Cu-PMO catalyst is effective on hydrogenolysis of low M.W. lignin fractions.•Catalyzed hydroprocessing can provide aromatic monomers of commercial interest.A copper-catalyzed depolymerization strategy was employed to investigate the impact of lignin structure on the distribution of hydroprocessing products. Specifically, lignin was extracted from beech wood and miscanthus grass. The extracted lignins, as well as a commercial lignin (P1000), were then fractionated using ethyl acetate to provide three different portions for each source of lignin [total of 9 fractions]. Each fraction was structurally characterized and treated with a copper-doped porous metal oxide (Cu-PMO) catalyst under 4 MPa H2 and at 180 °C for 12 h. The reaction conditions provided notable yields of oil for each fraction of lignin. Analysis of the oils indicated phenolic monomers of commercial interest. The structure of these monomers and the yield of monomer-containing oil was dependent on the origin of the lignin. Our results indicate that hydroprocessing with a Cu-PMO catalyst can selectively provide monomers of commercial interest by careful choice of lignin starting material.

The Twelve Principles of Green Chemistry were first published in 1998 and provide a framework that has been adopted not only by chemists, but also by design practitioners and decision-makers (e.g., materials scientists and regulators). The development of the Principles was initially motivated by the need to address decades of unintended environmental pollution and human health impacts from the production and use of hazardous chemicals. Yet, for over a decade now, the Principles have been applied to the synthesis and production of engineered nanomaterials (ENMs) and the products they enable. While the combined efforts of the global scientific community have led to promising advances in the field of nanotechnology, there remain significant research gaps and the opportunity to leverage the potential global economic, societal and environmental benefits of ENMs safely and sustainably. As such, this tutorial review benchmarks the successes to date and identifies critical research gaps to be considered as future opportunities for the community to address. A sustainable material design framework is proposed that emphasizes the importance of establishing structure–property–function (SPF) and structure–property–hazard (SPH) relationships to guide the rational design of ENMs. The goal is to achieve or exceed the functional performance of current materials and the technologies they enable, while minimizing inherent hazard to avoid risk to human health and the environment at all stages of the life cycle.

Green Chemistry is a relatively new emerging field that strives to work at the molecular level to achieve sustainability. The field has received widespread interest in the past decade due to its ability to harness chemical innovation to meet environmental and economic goals simultaneously. Green Chemistry has a framework of a cohesive set of Twelve Principles, which have been systematically surveyed in this critical review. This article covers the concepts of design and the scientific philosophy of Green Chemistry with a set of illustrative examples. Future trends in Green Chemistry are discussed with the challenge of using the Principles as a cohesive design system (93 references).