Adriana Olejniczak

Antimicrobial resistance is a current critical challenge, requiring the urgent development of new, effective broad-spectrum antimicrobials. To tackle this challenge, in this work, naturally occurring B vitamins, viz. nicotinamide, nicotinic acid and p-aminobenzoic acid, were used as precursors of both the cation and anion to design novel ionic liquids (ILs) in the form of quaternary ammonium salts (QASs). These combinations allowed for the development of multifunctional (anti-inflammatory and antimicrobial) agents targeting oral administration. The QASs were synthesized, characterized, and evaluated for the therapeutic potential as well as mechanism of the antimicrobial activity. Mixtures and cocrystals of the starting materials were also investigated for comparison purposes. Salts with the p-aminobenzoate anion showed excellent anti-inflammatory activity, inhibiting albumin denaturation by up to 54%, remarkably outperforming diclofenac sodium at its peak plasma concentration. Both albumin-based and in silico COX-2 studies further indicated that increasing the alkyl chain length significantly enhances the compounds’ efficacy. Antimicrobial tests showed that QASs were up to 250 times more effective than their non-ionic analogues. Moreover, the salts with the highest bactericidal activity completely inhibited biofilm growth against S. aureus and P. aeruginosa. Solubility studies under simulated gastrointestinal pH showed higher solubility of QASs, up to 100-fold, compared to the non-ionic forms. Cytotoxicity assay using human normal small intestinal cells (HIEC-6) revealed that even the most potent vitamin B analogues, were approximately ten times less toxic than the widely applied pharmaceutical agent, benzalkonium chloride. Ecotoxicity studies using A. franciscana also confirmed their low environmental impact.

Effective oral drug delivery requires compounds with suitable solubility, permeability, and physicochemical properties to ensure efficient absorption in the gastrointestinal tract. This study evaluates vitamin-derived quaternary ammonium salts (QASs) based on nicotinamide, nicotinic acid, and p-aminobenzoic acid, together with their nonionic counterparts, as potential orally administrable molecules. In silico pharmacokinetic predictions identified nicotinate QASs as the most promising candidates, exhibiting favorable permeability, intestinal absorption, and solubility profiles. PAMPA experiments confirmed high passive permeability for all compounds, with 6-hour Papp values exceeding 1.1·10⁻⁶ cm·s⁻¹, and demonstrated that membrane transport depends strongly on alkyl chain length and counterion identity. Permeability decreased notably for derivatives with octyl chains, whereas nicotinate QASs displayed values comparable to diclofenac sodium, and the shortest-chain p-aminobenzoate and its nonionic analogue slightly surpassed the reference drug. Surface activity analysis revealed that reductions in solution surface tension significantly enhance membrane transport, overriding limitations associated with increased molecular size. Overall, the synergistic influence of alkyl chain length, anion selection, and surface activity underscores the potential of vitamin-derived QASs as tunable, multifunctional candidates for oral drug development.

Following global trends, the main issue is to ensure that humanity can progress without harming the environment. This article outlines the synthesis of novel ionic liquids composed of an alkylbetaine cation, whose structure is based on glycine-betaine (a byproduct of sugar beet production) and an anion based on indole-3-butyric acid (a natural auxin found in plants). The article details the synthesis method used and demonstrates its negligible environmental impact. In addition, the main physicochemical properties of ionic liquids and their initial substrates have been assessed. Biological studies indicate that these ionic liquids effectively stimulate plant growth compared to the potassium salt of indole-3-butyric acid by approximately 40–60%, promoting positive effects on plant growth after sowing, while they may also contribute to seed protection before sowing. Furthermore, environmental studies have shown that these compounds are unlikely to pose a threat to freshwater and saltwater organisms, as they fall into the Practically Nontoxic to Slightly Toxic class in the case of A. franciscana and the Practically Nontoxic to Moderately Toxic class in the case of D. magna. Moreover, ionic liquids exhibited a benign effect on soil microorganisms, with toxic effects occurring only for salts containing the longest alkyl chains (MIC = 62.5–250 μg·cm^–3).

This study is focused on the utilization of naturally occurring salicylic acid and nicotinamide (vitamin B₃) in the development of novel sustainable Active Pharmaceutical Ingredients (APIs) with significant potential for treating acne vulgaris. The study highlights how the chemical structure of the cation significantly influences surface activity, lipophilicity, and solubility in aqueous media. Furthermore, the new ionic forms of APIs, the synthesis of which was assessed with Green Chemistry metrics, exhibited very good antibacterial properties against common pathogens that contribute to the development of acne, resulting in remarkable enhancement of biological activity ranging from 200 to as much as 2000 times when compared to salicylic acid alone. The molecular docking studies also revealed the excellent anti-inflammatory activity of N-alkylnicotinamide salicylates comparable to commonly used drugs (indomethacin, ibuprofen, and acetylsalicylic acid) and were even characterized by better IC₅₀ values than common anti-inflammatory drugs in some cases. The derivative, featuring a decyl substituent in the pyridinium ring of nicotinamide, exhibited efficacy against Cutibacterium acnes while displaying favorable water solubility and improved wettability on hydrophobic surfaces, marking it as particularly promising. To investigate the impact of the APIs on the biosphere, the EC₅₀ parameter was determined against a model representative of crustaceans─Artemia franciscana. The majority of compounds (with the exception of the salt containing the dodecyl substituent) could be classified as "Relatively Harmless" or "Practically Nontoxic", indicating their potential low environmental impact, which is essential in the context of modern drug development.

Esterquats constitute a unique group of quaternary ammonium salts (QASs) that contain an ester bond in the structure of the cation. Despite the numerous advantages of this class of compounds, only two mini-reviews discuss the subject of esterquats: the first one (2007) briefly summarizes their types, synthesis, and structural elements required for a beneficial environmental profile and only briefly covers their applications whereas the second one only reviews the stability of selected betaine-type esterquats in aqueous solutions. The rationale for writing this review is to critically reevaluate the relevant literature and provide others with a “state-of-the-art” snapshot of choline-type esterquats and betaine-type esterquats. Hence, the first part of this survey thoroughly summarizes the most important scientific reports demonstrating effective synthesis routes leading to the formation of both types of esterquats. In the second section, the susceptibility of esterquats to hydrolysis is explained, and the influence of various factors, such as the pH, the degree of salinity, or the temperature of the solution, was subjected to thorough analysis that includes quantitative components. The next two sections refer to various aspects associated with the ecotoxicity of esterquats. Consequently, their biodegradation and toxic effects on microorganisms are extensively analyzed as crucial factors that can affect their commercialization. Then, the reported applications of esterquats are briefly discussed, including the functionalization of macromolecules, such as cotton fabric as well as their successful utilization on a commercial scale. The last section demonstrates the most essential conclusions and reported drawbacks that allow us to elucidate future recommendations regarding the development of these promising chemicals.

Esterquats constitute a unique group of quaternary ammonium salts (QASs) that contain an ester bond in the structure of the cation. Despite the numerous advantages of this class of compounds, only two mini-reviews discuss the subject of esterquats: the first one (2007) briefly summarizes their types, synthesis, and structural elements required for a beneficial environmental profile and only briefly covers their applications whereas the second one only reviews the stability of selected betaine-type esterquats in aqueous solutions. The rationale for writing this review is to critically reevaluate the relevant literature and provide others with a “state-of-the-art” snapshot of choline-type esterquats and betaine-type esterquats. Hence, the first part of this survey thoroughly summarizes the most important scientific reports demonstrating effective synthesis routes leading to the formation of both types of esterquats. In the second section, the susceptibility of esterquats to hydrolysis is explained, and the influence of various factors, such as the pH, the degree of salinity or the temperature of the solution, was subjected to thorough analysis that includes quantitative components. The next two sections refer to various aspects associated with the ecotoxicity of esterquats. Consequently, their biodegradation and toxic effects on microorganisms are extensively analyzed as crucial factors that can affect their commercialization. Then, the reported applications of esterquats are briefly discussed, including functionalization of macromolecules, such as cotton fabric as well as their successful utilization on a commercial scale. The last section demonstrates the most essential conclusions and reported drawbacks that allow us to elucidate future recommendations regarding the development of these promising chemicals.

Lately, ionic forms (namely, quaternary ammonium salts, QASs) of nicotinamide, widely known as vitamin B₃, are gaining popularity in the sectors developing novel pharmaceuticals and agrochemicals. However, the direct influence of these unique QASs on the development of various terrestrial plants, as well as other organisms, remains unknown. Therefore, three compounds comprising short, medium, and long alkyl chains in N-alkylnicotinamide were selected for phytotoxicity analyses, which were conducted on representative dicotyledonous (white mustard) and monocotyledonous (sorghum) plants. The study allowed the determination of the impact of compounds on the germination capacity as well as on the development of roots and stems of the tested plants. Interestingly, independently of the length of the alkyl chain or plant species, all QASs were established as non-phytotoxic. In addition, QSAR simulations, performed using the EPI Suite™ program pack, allowed the determination of the products’ potential toxicity toward fish, green algae, and daphnids along with the susceptibility to biodegradation. The obtained nicotinamide derivative with the shortest chain (butyl) can be considered practically non-toxic according to GHS criteria, whereas salts with medium (decyl) and longest (hexadecyl) substituent were included in the ‘acute II’ toxicity class. These findings were supported by the results of the toxicity tests performed on the model aquatic plant Lemna minor. It should be stressed that all synthesized salts exhibit not only a lack of potential for bioaccumulation but also lower toxicity than their fully synthetic analogs.

The use of chemicals for various purposes in agriculture has numerous consequences, such as the contamination of ecosystems. Thus, nowadays it is perceived that their development should adhere to the principles of green chemistry elaborated by Paul Anastas. Consequently, to create more environment-friendly herbicides, we elaborated a ‘green’ synthesis method of a series of ionic liquids (ILs) containing cations derived from glycine. The appropriately modified cations were combined with an anion from the group of phenoxy acids, commonly known as 2,4-DP. The products were obtained with high yields, and subsequently, their properties, such as density, viscosity and solubility, were thoroughly examined to elucidate existing structure–property relationships. All ILs were liquids at room temperature, which enabled the elimination of some serious issues associated with solid active forms, such as the polymorphism or precipitation of an active ingredient from spray solution. Additionally, the synthesized compounds were tested under greenhouse conditions, which allowed an assessment of their effectiveness in regulating the growth of oilseed rape, selected as a model dicotyledonous plant. The product comprising a dodecyl chain exhibited the greatest reduction in the fresh weight of plants, significantly surpassing not only a commercially used reference herbicide but also the potassium salt of 2,4-DP.