Chloromethylation of Lignin as a Route to Functional Material with Catalytic Properties in Cross-Coupling and Click Reactions.

Invited for this issue's cover are researchers from Tallinn University of Technology (TalTech). The image depicts the lignin chemical evolution route from raw biomass through a greener chloromethylation procedure developed by the research team. It showcases the transformation into lignin-supported metal nanoparticles, serving as a catalyst for various chemical reactions in both batch and continuous flow conditions. The Research Article itself is available at 10.1002/cssc.202301588.

Chloromethylation of Lignin as a Route to Functional Material with Catalytic Properties in Cross-Coupling and Click Reactions.

We present a novel, greener chloromethylation procedure for organosolv aspen lignin under mild reaction conditions without Lewis acid as a catalyst and in acetic acid as a solvent. This synthetic protocol provides a reliable approach to chloromethylated lignin (CML) and means to obtain valuable lignin derivatives. The resulted CML was subsequently transformed into 1-methylimidazolium lignin (ImL), which effectively serves as a stabilizing agent for Pd/CuO nanoparticles (Pd/CuO-NPs). To evaluate the versatility of developed lignin-based catalyst, we investigate its performance in a series of carbon-carbon bond formation reactions, including Suzuki-Miyaura, Sonogashira, Heck reactions, and azide-alkyne cycloaddition (click) reaction. Remarkably, this catalyst exhibited a high degree of catalytic efficiency, resulting in reactions with yields ranging from average to excellent. The heterogeneous catalyst demonstrated outstanding recyclability, enabling its reuse for at least 10 consecutive reaction cycles, with yields consistently falling within the range of 42 % to 84 %. A continuous flow reactor cartridge prototype employing Lignin@Pd/CuO-NPs was developed, yielding results comparable to those achieved in batch reactions. The utilization of Lignin@Pd/CuO-NPs as a catalyst showcases its potential to facilitate diverse carbon-carbon bond formation reactions and underscores its promising recyclability, aligning with the green chemistry metrics and principles of sustainability in chemical processes.

Sustainable ionic liquids-based molecular platforms for designing acetylcholinesterase reactivators.

We report a green chemistry approach for preparation of oxime-functionalized ILs as AChE reactivators: amide/ester linked IL, l-alanine, and l-phenylalanine derived salts bearing pyridinium aldoxime moiety. The reactivation capacities of the novel oximes were evaluated towards AChE inhibited by typical toxic organophosphates, sarin (GB), VX, and paraoxon (PON). The studied compounds are mostly non-toxic up to the highest concentrations screened (2 mM) towards Gram-negative and Gram-positive bacteria cell lines and both filamentous fungi and yeasts in the in vitro screening experiments as well as towards the eukaryotic cell (CHO-K1 cell line). Introduction of the oxime moiety in initially biodegradable structure decreases its ability to biodegradation. The compound 3d was shown to reveal remarkable activity against the AChE inhibited by VX, exceeding conventional reactivators 2-PAM and obidoxime. The regularities on antidotal activity, cell viability, plasma stability, biodegradability as well as molecular docking study of the newly synthesized oximes will be used for further improvement of their structures.

Synergistic antibacterial effect of copper and silver nanoparticles and their mechanism of action.

Bacterial infections are one of the leading causes of death worldwide. In the case of topical bacterial infections such as wound infections, silver (Ag) has historically been one of the most widely used antibacterials. However, scientific publications have demonstrated the adverse effects of silver on human cells, ecotoxicity and insufficient antibacterial effect for the complete elimination of bacterial infections. The use of Ag in the form of nanoparticles (NPs, 1-100 nm) allows to control the release of antibacterial Ag ions but is still not sufficient to eliminate infection and avoid cytotoxicity. In this study, we tested the potency of differently functionalized copper oxide (CuO) NPs to enhance the antibacterial properties of Ag NPs. The antibacterial effect of the mixture of CuO NPs (CuO, CuO-NH2 and CuO-COOH NPs) with Ag NPs (uncoated and coated) was studied. CuO and Ag NP combinations were more efficient than Cu or Ag (NPs) alone against a wide range of bacteria, including antibiotic-resistant strains such as gram-negative Escherichia coli and Pseudomonas aeruginosa as well as gram-positive Staphylococcus aureus, Enterococcus faecalis and Streptococcus dysgalactiae. We showed that positively charged CuO NPs enhanced the antibacterial effect of Ag NPs up to 6 times. Notably, compared to the synergy of CuO and Ag NPs, the synergy of respective metal ions was low, suggesting that NP surface is required for the enhanced antibacterial effect. We also studied the mechanisms of synergy and showed that the production of Cu+ ions, faster dissolution of Ag+ from Ag NPs and lower binding of Ag+ by proteins of the incubation media in the presence of Cu2+ were the main mechanisms of the synergy. In summary, CuO and Ag NP combinations allowed increasing the antibacterial effect up to 6 times. Thus, using CuO and Ag NP combinations enables to retain excellent antibacterial effects due to Ag and synergy and enhances beneficial effects, since Cu is a vital microelement for human cells. Thus, we suggest using combinations of Ag and CuO NPs in antibacterial materials, such as wound care products, to increase the antibacterial effect of Ag, improve safety and prevent and cure topical bacterial infections.

Sustainable Phenylalanine-Derived SAILs for Solubilization of Polycyclic Aromatic Hydrocarbons.

The solubilization capacity of a series of sustainable phenylalanine-derived surface-active ionic liquids (SAILs) was evaluated towards polycyclic aromatic hydrocarbons-naphthalene, anthracene and pyrene. The key physico-chemical parameters of the studied systems (critical micelle concentration, spectral properties, solubilization parameters) were determined, analyzed and compared with conventional cationic surfactant, CTABr. For all studied PAH solubilization capacity increases with extension of alkyl chain length of PyPheOCn SAILs reaching the values comparable to CTABr for SAILs with n = 10-12. A remarkable advantage of the phenylalanine-derived SAILs PyPheOCn and PyPheNHCn is a possibility to cleave enzymatically ester and/or amide bonds under mild conditions, to separate polycyclic aromatic hydrocarbons in situ. A series of immobilized enzymes was tested to determine the most suitable candidates for tunable decomposition of SAILs. The decomposition pathway could be adjusted depending on the choice of the enzyme system, reaction conditions, and selection of SAILs type. The evaluated systems can provide selective cleavage of the ester and amide bond and help to choose the optimal decomposition method of SAILs for enzymatic recycling of SAILs transformation products or as a pretreatment towards biological mineralization. The concept of a possible practical application of studied systems for PAHs solubilization/separation was also discussed focusing on sustainability and a green chemistry approach.

Biobased natural deep eutectic system as versatile solvents: Structure, interaction and advanced applications.

The increasing emphasis on the development of green replacements to traditional organic solvents and ionic liquids (ILs) can be attributed to the rising concerns over human health and detrimental impacts of conventional solvents towards the environment. A new generation of solvents inspired by nature and extracted from plant bioresources has evolved over the last few years, and are referred to as natural deep eutectic solvents (NADES). NADES are mixtures of natural constituents like sugars, polyalcohols, sugar-based alcohols, amino acids and organic acids. Interest in NADES has exponentially grown over the last eight years, which is evident from an upsurge in the number of research projects undertaken. NADES are highly biocompatible as they can be biosynthesized and metabolized by nearly all living organisms. These solvents pose several noteworthy advantages, such as easy synthesis, tuneable physico-chemical properties, low toxicity, high biodegradability, solute sustainability and stabilization and low melting point. Research on the applicability of NADES in diverse areas is gaining momentum, which includes as - media for chemical and enzymatic reactions; extraction media for essential oils; anti-inflammatory and antimicrobial agent; extraction of bioactive composites; as chromatographic media; preservatives for labile compounds and in drug synthesis. This review gives a complete overview of the properties, biodegradability and toxicity of NADES which we propose can assist in further knowledge generation on their significance in biological systems and usage in green and sustainable chemistry. Information on applications of NADES in biomedical, therapeutic and pharma-biotechnology fields is also highlighted in the current article along with the recent progress and future perspectives in novel applications of NADES.

N-substituted arylhydroxamic acids as acetylcholinesterase reactivators.

The problem of the efficient treatment of acute organophosphorus (OP) poisoning needs more efforts in the development of a versatile antidote, applicable for treatment of the injuries of both peripheral and central nervous systems. A series of N-H, N-methyl, N-butyl, and N-phenyl derivatives of benzhydroxamic (1a-1d), 3-methoxybenzhydroxamic (2a-2d), 4-methoxybenzhydroxamic (3a-3d) acids, and corresponding salycilhydroxamates (4a-4d) was prepared. Their predicted hydrophobicity (log P) was evaluated as regards to ВВВ score by the open access cheminformatics tools; prediction of the passive transport across the BBB was found by means on the parallel artificial membrane permeability assay (PAMPA). The data on reactivation capacity of human acetylcholinesterase (HssAChE) inhibited by GB, VX, and paraoxon was supported by molecular docking study on binding to the active site of the AChE, viability study against mammalian cells (Chinese hamster ovary CHO-K1), and biodegradability (Closed Bottle test OECD 301D). Among the studied compounds, N-butyl derivatives have better balanced combination of properties; among them, N-butylsalicylhydroxamic acid is most promising. The studied compounds demonstrate modest reactivation capacity; change of N-H by N-Me ensures the reactivation capacity in studied concentrations on all studied OP substrates; among N-butyl derivatives, the N-butylsalicylhydroxamic acid demonstrates most promising results within the series. The found regularities may lead to selection of perspective structures to complement current formulations for medical countermeasures against poisoning by organophosphorus toxicants.

Development of Functional Composite Cu(II)-Polyoxometalate/PLA with Antimicrobial Properties.

Novel composite self-disinfecting films of polylactic acid (PLA) filled with nanosized particles of double sodium-copper(II) paratungstate B Na2Cu3(CuOH)2[W12O40(OH)2]·32H2O (POM) were developed. The solvent casting (POM/PLA film) and solvent-free melt extrusion methods (Extr. POM/PLA film) were applied for film preparation. The copper (II) ion release to water from both types of the films after 10 days at different temperatures demonstrated that the PLA matrix acts as a diffusion barrier, and the resulting concentration of released copper in water at room temperature remained low, at 0.79% for POM/PLA film and 0.51% for Extr. POM/PLA film. The POM-containing films reveals a significant inhibitory effect against E. coli ATCC 25922 in the agar diffusion test. The numbers of CFUs in washes of the films after incubation for 24 h were found to be 3.6 log CFU mL-1 (POM/PLA film) and 4.1 log CFU mL-1 (Extr. POM/PLA film). The films combine the antibacterial properties of POM and a bio-based polymer matrix, which makes them a prospective coating material for applications in hospital indoor environments. Excellent thermal stability of POM gives a technological advantage for industrial manufacturing to allow the processing of novel composite material in the solvent free (molten) state.

Ionic liquid based pretreatment of lignocellulosic biomass for enhanced bioconversion.

Lignocellulosic biomass is the most plentiful renewable biomolecule and an alternative bioresource for the production of biofuels and biochemicals in biorefineries. But biomass recalcitrance is a bottleneck in their usage, thus necessitating their pretreatment for hydrolysis. Most pretreatment technologies, result in toxic by-products or have lower yield. Ionic liquids (ILs) have successfully advanced as 'greener and recyclable' alternatives to volatile organic solvents for lignocellulosic biomass dissolution. This review covers recent developments made in usage of IL-based techniques with focus on biomass breakdown mechanism, process parameter design, impact of cation and anion groups, and the advantageous impact of ILs on the subsequent processing of the fractionated biomass. Progress and barriers for large-scale commercial usage of ILs in emerging biorefineries were critically evaluated using the principles of economies of scale and green chemistry in an environmentally sustainable way.

Toxicity profiling of 24 l-phenylalanine derived ionic liquids based on pyridinium, imidazolium and cholinium cations and varying alkyl chains using rapid screening Vibrio fischeri bioassay.

A library of 24 pyridinium-, imidazolium-, and cholinium-based ionic liquids (ILs) with varying alkyl chain from C2 to C16 was toxicologically profiled using naturally luminescent marine bacteria Vibrio fischeri. The toxicity (30-min EC50) of studied ILs to Vibrio fischeri ranged from 7.82 µM (4.2 mg/L) (PyC12Phe) to 3096 µM (1227 mg/L) (ImidC2Phe), i.e. from "toxic" (EC50 1-10 mg/L) to "not harmful" (EC50 > 100 mg/L). Inhibition of the bacterial luminescence upon 30-min exposure to ILs correlated well with bacterial viability (exposure for 4 h). The toxicity of studied ILs was largely driven by the length of the alkyl chain (hydrophobicity) and not the type of cationic part of the IL: starting from C10 all the ILs irrespective of the cationic part proved "toxic". The toxicity of the studied ILs was increasing in parallel to their hydrophobicity up to log Kow = 1 (C8-C10) and then levelling up, being consistent with the previously obtained analogous data sets. The "cut-off" effect reported in this study for longer chain length members of the ILs series leads to the "limit" toxicity level for this type of ILs to be ca. 8 mM. Two open-access online tools (www.molinspiration.com and www.vcclab.org) have been applied for the calculation of the Kow values for the 24 ILs reported in this study and 21 ILs reported in the literature. This lead to plotting two nonlinear monotonic correlations between the values of experimental log (1/EC50) and calculated log Kow. The limitation of the online tools and an effect of the ILs structure on the "cut-off" effect have been discussed. The challenge of developing low microbial toxicity surface active ILs remains a significant task to overcome. Our results shed light on the new approaches for designing environmentally benign ILs and functional surfactants. As the hydrophobicity of the ILs significantly correlated with the toxicity, the Vibrio fischeri assay could be considered a powerful tool in providing toxicity data for building and evaluating the QSAR toxicity models for ILs.

From α-nucleophiles to functionalized aggregates: exploring the reactivity of hydroxamate ion towards esterolytic reactions in micelles.

Owing to the rising threats of neurotoxic organophosphosphorus compounds, facile and efficient decontamination systems are required. Since the last few decades, the search for promising α-nucleophiles for straightforward and eco-friendly decontamination reactions using α-nucleophiles has been considerably boosted up. Among these, hydroxamic acids have been widely studied due to their potential α-nucleophilicity towards carbon and phosphorus based esters. This account summarizes our research on α-nucleophilicity of hydroxamate ions in water and micelles towards esterolytic reactions. Efforts of our group in the last few years have been collectively judged and compared with the crucial findings of researchers in the relevant field. The present article sheds light on the rich chemistry of the hydroxamate ion as a perfect candidate to degrade organophosphorus esters (i.e. nerve agents, pesticides and their simulants) in water, in micelles of conventional surfactants, and in functionalized micelles. The current report also provides an insight into the possible nature and mechanisms of these reactions. A brief account of the biological activities of hydroxamic acids that have recently spurred research in medicine against some fatal diseases has been included.

The micellar and surface properties of a unique type of two-headed surfactant--pentaerythritol based di-cationic surfactants.

The surface properties of some families of cationic two-headed surfactants based on a pentaerythritol backbone are described. The compounds have the following general structure (1), where R' are head groups and R are linear alkyl groups ranging from octyl to tetradecyl. The syntheses of these compounds has been published in detail previously. Critical micelle concentrations (cmc values) of these two-headed surfactants have been determined and compared to conventional ionic surfactants and gemini surfactants of similar structure. In addition, the surface activity of these two-headed surfactants, expressed as the C20 value and the surface tension at the cmc, have been determined. Transmission electron microscopy has been used to examine the morphology of the aggregates formed by these amphiphiles. In general, when compared to conventional ionic and two-headed surfactants, these new two-headed surfactants exhibit a remarkable efficiency in the tendency to self-assemble and are significantly more surface active than their conventional counterparts [structure: see text].

Physicochemical properties and supernucleophilicity of oxime-functionalized surfactants: hydrolytic catalysts toward dephosphorylation of di- and triphosphate esters.

Aggregation and kinetic studies have been performed to understand the hydrolytic potencies of the series of oxime-functionalized surfactants, viz., 3- hydroxyiminomethyl-1-alkylpyridinium bromide (alkyl = CnH2n+1, n = 10, 12, 14, 16, 18) in the cleavage of phosphate esters, p-nitrophenyl diphenyl phosphate (PNPDPP) and bis(2,4-dinitrophenyl) phosphate (BNDPP), in mixed micelles with cetylpyridinium bromide (CPB). Micellization and surface properties of mixed micelles functional surfactants with CPB were studied by conductivity and surface tension measurements. Acid dissociation constants (pKa) were determined, the effect of functional surfactant alkyl chain length and pH on the observed rate constant (kobs) for phosphate ester cleavage has been discussed, and the effect of substrate on the supernucleophilicities of the studied oximes was monitored. Functionalized oxime-based surfactants were proved to be supernucleophiles to attack on the P═O center of tri- and diphosphate esters. Oximes with hexadecyl alkyl chain length (3-C16) showed maximum micellar effect on the rate constants toward PNPDPP. Micellar effects were analyzed in terms of the pseudophase model.

Functionalized vesicles based on amphiphilic boronic acids: a system for recognizing biologically important polyols.

We report on a new approach for creating water-soluble functionalized vesicles employing N-alkyl-3-boronopyridinium triflates (alkyl = Me, C12H25, C16H33) as sensors for monosaccharides. The nanoaggregate properties were studied by means of DLS, TEM, high-resolution (1)H NMR, and the solvatochromic dyes Reichardt's betaine and Methyl Orange. The vesicles were shown to have 30-200 nm diameters depending on the amphiphile chain length. Diol binding to the vesicles was studied by steady-state fluorescence and UV-vis using Alizarin Red S as a probe in the solution at pH 7.4 in the presence and in the absence of D-glucose and D-fructose. Strong sensing ability of boronic acid functional moieties in the order D-fructose > D-glucose was demonstrated, and apparent binding constants were estimated.

Effect of Hofmeister and alkylcarboxylate anionic counterions on the Krafft temperature and melting temperature of cationic gemini surfactants.

The effect of counterions was investigated to probe the principal ionic effects on the solubility in water and melting behavior of cationic gemini surfactants. We focused on two types of counterions: (1) small inorganic counterions that are typically taken from the Hofmeister series were studied to focus on the effect of ion type and (2) n-alkylcarboxylate counterions were studied to focus on the effect of the hydrophobicity of counterions. The Krafft temperature (Tk) and melting temperature (Tm) were obtained by conductivity measurements, calorimetric measurements, and optical microscopy observation. The results clearly indicate that Tk, which represents the solubility of surfactants, is not determined by a single parameter of ions such as the hydration free energy, as is too often assumed, but rather by the combined effects between the hydrophobicity of anions associated with other effects such as the polarizability, dehydrated ion size, and ionic morphology. In parallel, our observation demonstrated that all of the surfactants showed a transition from a crystalline phase to a thermotropic liquid-crystalline phase at around ca. 70 °C, which transformed to an isotropic liquid phase at around ca. 150 °C, and that the transition temperatures depended strongly on the counterion type. The counterion effects on the solubilization and melting behaviors were then compared with micellization properties that have been reported previously. These results provide new insight into understanding the effect of ions on the delicate balance of forces controlling the solution properties and aggregate morphology of charged amphiphilic molecules. Specifically, the solubilization properties of these cationic surfactants with various counterions were determined mainly by the subtle interplay between the hydration of counterions and the dissociation energies (stability of crystallinity) of the ion pair.

Counteranion effect on micellization of cationic gemini surfactants 14-2-14: Hofmeister and other counterions.

The effect of counterions was investigated and analyzed to probe the principal ionic effects influencing the micellization behavior of dimeric cationic surfactant ethanediylbis(dimethyltetradecylammonium), referred to as gemini 14-2-14. The 30 counterions were classified to four different families depending on their nature: (1) small and inorganic counterions which are typically taken from the Hofmeister series were studied to focus on the effect of ion type; (2) n-alkyl carboxylate counterions were studied to focus on the effect of the hydrophobicity of counterions; (3) aromatic carboxylate counterions were included to focus on the effect of the position of substitutions; and (4) other counterions were included in order to shed light on other parameters. By investigating the critical micelle concentration (CMC), ionization degree of micelle (alpha), free energy of micellization (DeltaG(M)), and aggregation numbers N of the gemini surfactant with these different types of anions, we demonstrated the effect of different ion properties independently. This approach allowed us to describe the effect of counterions on the micellization behavior of the gemini surfactant in terms of complex interplay between hydrophobicity of anions and other ion properties such as counterion hydration, interfacial packing of ions, and ionic morphology. Indeed, our results clearly demonstrate that a counterion effect on micellization properties cannot be described as a result of one single parameter of ions, as is too often assumed, but rather the balancing effects cooperatively affect the propensity of counterions to form ion pairs with surfactant headgroups and the entropy gain upon micellization. These results provide new insight in understanding the effect of ions on the delicate balance of forces controlling aggregate morphology and solution properties of charged amphiphilic molecules.