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Gemini surfactants, also called Gemini, especially those with quaternary ammonium head groups, are recognized for their distinctive aggregation behavior and enhanced structure-activity relationships. The unique dual-head and dual-tail structure of Gemini grants them superior surface activity, allowing them to effectively lower surface and interfacial tension. To investigate the self-assembly behavior and surface-active properties that make them suitable as anticorrosion and antimicrobial agents, a series of cationic Gemini featuring amide bonds and varying alkyl chain lengths were synthesized. Surface activity and self-assembly characteristics of these cationic Gemini were analyzed using methods such as surface tension, electrical conductivity, fluorescence, and isothermal titration calorimetry. The findings revealed that these Gemini possess enhanced surface-active and self-assembly properties in comparison to traditional single-tail, monoheaded surfactants. Thermodynamic studies confirmed that these Gemini self-assemble spontaneously in water above a relatively low threshold concentration, with the self-assembly process becoming less favorable as the alkyl chain length decreased. The length of the chains also affected the size and shape of the aggregates formed. These Gemini have been shown to exhibit remarkable anticorrosion properties on steel surface. The performance of these compounds as corrosion inhibitors showed a clear dependence on chain length, with the shortest chain length Gemini providing the highest inhibition efficiency. These Gemini have also exhibited pronounced antibacterial activities against Escherichia coli (DH5alpha) and Staphylococcus aureus bacteria.

The rising threat of antimicrobial-resistant (AMR) infections highlights the urgent need for effective antimicrobial agents and therapies. Peptide-based antimicrobial nanomaterials are well-placed to meet this need. Here, we explore the conjugation of antimicrobial gemini quaternary ammonium compounds (GQAs) with designed short hexapeptides to create cationic antimicrobial nanomaterials with low cytotoxicity and minimal resistance tendency. (WA) 3 GQA8C self-assembles into nanoparticles and exhibits potent antimicrobial activity against drug-resistant pathogens and enhanced stability. (WA) 3 GQA8C protects against subcutaneous abscess infection and rescues mice from acute peritonitis infection by reducing the systemic bacterial burden and alleviating organ damage, with superior effects to vancomycin. Notably, (WA) 3 GQA8C thoroughly disrupts bacterial membrane integrity akin to peeling fruit to induce bacterial membrane disintegration, a feat inaccessible to conventional antibiotics. Mechanistic studies suggest that (WA) 3 GQA8C targets the bacterial membrane phospholipids phosphatidylglycerol (PG), inducing PG deformation to form fibrous or lamellar structures, which leads to the disruption of the bacterial membrane. Furthermore, the interference in lipoprotein trafficking exacerbates damage to bacterial membrane integrity. (WA) 3 GQA8C also synergizes antimicrobial activity by impairing the protein synthesis function of the ribosome. These quaternized peptide nanoassemblies provide a rational strategy for designing peptide-based antimicrobial nanomaterials to combat the growing threats of resistant bacteria.

Quaternary ammonium compounds (QACs) have been essential for protecting human health for almost a century, functioning as surface disinfectants and sanitizers. With bacterial resistance increasing against commercially available QACs, the development of novel antimicrobials with divergent architectures is essential for effective infection prevention and control. Toward this end, our group has expanded beyond traditional ammonium scaffolds and explored the development of quaternary phosphonium compounds (QPCs). Herein, we report the synthesis and biological investigation of a series of 20 novel multicationic QPCs, bearing multiple short alkyl or aryl chains, also referred to as "bushy-tailed" multiQPCs; these structures were hypothesized to have strong bioactivity while displaying low mammalian toxicity. Select bushy-tailed QPC derivatives with trishexylphosphonium groups displayed single-digit or sub-micromolar activity against all seven bacteria tested, and MIC values of 2- to 8-fold better than their bushy-tailed QAC counterparts. Importantly, therapeutic indices of these bushy-tailed QPCs were favorable in many cases, and were ≥4 against the entire bacterial panel for pX-P6*,P6* and 1,8-P6*,P6*, superior to more traditional architectures. This work highlights the promise of a novel set of multicationic phosphonium compounds as novel disinfectants with potent bioactivities and low toxicity., (© 2024 Wiley-VCH GmbH.)

In the pressing quest of novel treatments for chronic pain, α7 nAChR silent agonists show efficacy as anti-inflammatory modulators and represent a promising strategy. Recent findings reveal that a sulfonium ion can replace the quaternary ammonium nitrogen as an alternative pharmacophore for nAChR silent activation. This study reports the design, synthesis, and electrophysiological evaluation of a new series of sulfonium-based derivatives inspired by the archetypal silent agonist NS6740. Our findings identify NSS-9 as a novel sulfonium α7 silent agonist that effectively alleviates inflammatory pain in a mouse model, highlighting it as a lead compound for further optimization. These results provide insights into the potential of the sulfonium group as a chemotype interacting with the α7 binding site, making it a valuable scaffold for novel α7 silent agonists. Additionally, sulfonium compounds were tested on α9 nAChR, also involved in the cholinergic anti-inflammatory system, identifying one partial agonist and two antagonists.

Antibody-drug conjugates (ADCs) with camptothecin derivatives as payloads have been a hot topic of interest and research since the launch of DS-8201a. As an important component of ADCs, the adequate stability of the linker during circulation and its rapid release at the target site are crucial for the efficient efficacy of ADCs. Although traditional quaternary ammonium ADCs based on dipeptide linkers were highly stable and could be released by specific enzymes, their poor in vitro anti-tumor activity had limited their further exploration. We applied a methylsulfonylethylamine-modified MAC self-elimination system to a valine-alanine linker and constructed a quaternary ammonium ADC (HER2-11) that combines both stability and cleavability. The optimization of the linker effectively improved the in vitro cellular activity of conventional quaternary ammonium ADCs, but the complex intracellular cleavage mechanism of HER2-11 resulted in a weaker anti-tumor activity compared to HER2-GGFG-DXd, which provides great reference value for the continued research of this type of linker in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Purpose: Corneal pain is one of the most common eye symptoms caused by various types of epithelial injuries, including traumatic abrasion, chemical injury, ulcers, ultraviolet exposure, and infection. However, current therapeutic options for corneal pain are limited. In this study, we synthesized a novel quaternary ammonium compound, N-propylamiodarone bromide (NPA), and employed a rodent model of corneal injury to investigate whether NPA offers prolonged corneal analgesia through transient receptor potential vanilloid 1 (TRPV1) channel-mediated selective cellular entry, without hindering corneal epithelial recovery., Methods: In the corneal injury model, 24 adult Wistar rats received a topical application of normal saline, oxybuprocaine, or NPA (n = 8 each), and corneal pain sensitivity was assessed using the von Frey technique. Another set of 32 rats with intact corneas received oxybuprocaine, capsaicin (a TRPV1 agonist), or NPA with or without capsaicin (n = 8 each), followed by a mechanical sensitivity evaluation. Potential adverse effects on normal epithelial recovery were evaluated using fluorescence and hematoxylin-eosin staining in an additional 8 rats with corneal injury., Results: In the corneal injury model, NPA produced significantly longer-lasting analgesia than oxybuprocaine (duration of the maximum effect: 215 ± 11 vs 25 ± 2 min, P < 0.001). None of the animals presented any signs of eye irritability. In contrast to injured eyes, NPA alone did not significantly increase mechanical sensitivity in naïve eyes. However, the co-administration of NPA and capsaicin produced significantly longer-lasting corneal anesthesia than oxybuprocaine (duration of the maximum effect: 165 ± 15 vs 31 ± 2 min, P < 0.001). NPA did not hamper wound healing., Conclusion: The novel quaternary ammonium NPA produced long-lasting analgesia against corneal injury without hampering corneal recovery, suggesting that it is a potential candidate for analgesic medicine targeting corneal pain., Competing Interests: Masakazu Kotoda is named as the inventor on a patent pending covering the design and use of NPA (application number: 2023-146529). The other authors declare that no competing interests exist., (© 2024 Kotoda et al.)

The liposomal systems proved remarkably useful for the delivery of genetic materials but enhancing their efficacy remains a significant challenge. While structural alterations could result in the discovery of more effective transfecting lipids, improving the efficacy of widely used lipid carriers is also crucial in order to compete with viral vectors for gene delivery. Herein, we developed formulations of commercially available lipid, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) with synthetic amino acid based cationic lipids. Two cationic lipids were synthesized using amino acids, with either cystine (CTT) or arginine (AT) in the head group. These lipids were used to formulate co-liposomal structures with different lipid compositions. The liposomal formulations were broadly categorised into two types: amino acid-based liposomes without DOTAP (CTTD and ATD) and those with DOTAP (DtATD and DtCTTD). Optimized lipid-DNA complexes of DOTAP-incorporated formulations (DtATD and DtCTTD) exhibited enhanced efficacy in transfection compared to formulations lacking DOTAP as well as commercial formulations such as DOTAP:DOPE. Notably, DtCTTD displayed superior transfection capabilities in prostate cancer (PC3) and lung cancer (A549) cell lines when compared to the widely used commercial transfection reagent, Lipofectamine. Collectively, the findings from this study suggest that DOTAP-incorporated formulations derived from amino acid-based liposomes, hold promise as effective tools for improving transfection efficacy with reduced toxicity, offering potential advancements in gene delivery applications., (© 2024 Wiley-VCH GmbH.)

Chitosan derivatives, including O-carboxymethyl chitosan (CMC), N-(2-hydroxypropyltrimonium chloride)-O-carboxymethyl chitosan (QCMC), and N-(2-hydroxypropyltrimonium chloride)-O-dodecylylpyridine chitosan quaternary ammonium salt (DQCMC), were synthesized and characterized using Fourier transform infrared (FTIR) spectroscopy, 1 H nuclear magnetic resonance ( 1 H NMR) spectroscopy, Ultraviolet-visible (UV-vis) spectroscopy, and element analysis (EA). The antibacterial activities of chitosan and chitosan derivatives against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were evaluated through the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and antibacterial rate assays. Results demonstrated that DQCMC exhibited significantly higher antibacterial efficacy compared to chitosan, CMC, and QCMC. The MIC of DQCMC against E. coli and S. aureus were 31 μg/mL and 7 μg/mL, respectively, with a 100 % antibacterial rate at a concentration of 0.5 mg/mL. Furthermore, assessment of mouse fibroblast (L929) cell viability using cell counting kit-8 (CCK-8) methods revealed no toxicity associated with the material., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Multidrug-resistant (MDR) Gram-negative bacteria infections have gradually become a more serious health problem recently, and antibacterial drugs are urgently needed to tackle MDR Gram-negative bacteria. Herein, we synthesized a series of quaternary ammonium salt derivatives of hyperbranched polylysine (HPL- Cm - n ) with different alkyl chain lengths ( m = 4, 8, 12, 16) and grafting ratios ( n = 5.8-21.0) of alkyl quaternary ammonium salts ( Cm ). HPL- Cm - n s exhibited excellent antibacterial activities against drug-sensitive E. coli and P. aeruginosa , and specifically, HPL-C12- n s were also highly active against MDR E. coli and P. aeruginosa . The cytotoxicity and hemolytic activity of HPL- Cm - n s increased with the increase in the alkyl chain length and the grafting ratio of Cm . The killing study proved that HPL-C12-9.5 had fast killing kinetics and was bactericidal toward both drug-sensitive and MDR E. coli . The mechanistic studies showed that, similar to hyperbranched polylysine (HPL), HPL-C12-9.5 killed bacteria by disrupting the cell membranes and causing leakage of the cytoplasmic contents. HPL-C12- n s might have potential as an antibacterial agent to combat MDR Gram-negative bacteria.

In this study, a series of novel β-carboline condensed imidazolium derivatives (7a-7y) were designed and synthesized by incorporating imidazolium salt structures into β-carboline. The cytotoxicity of compounds 7a-7y was evaluated in various cancer cell lines, including lung cancer (A549), gastric cancer (BGC-823), mouse colon cancer (CT-26), liver cancer (Bel-7402), and breast cancer (MCF-7), using the MTT assay. Most compounds exhibited significant activity against one or more of the cancer cell lines. Notably, compounds 7 g, 7o, 7r, 7 s, 7u, 7v, 7x, and 7w showed the highest cytotoxic activity (IC 50  < 2 μM) in the tested tumor cell lines. Compound 7x demonstrated cytotoxic activities of 1.3 ± 0.3 μM (for BGC-823), 2.4 ± 0.4 μM (against A549), 7.8 ± 0.9 μM (for Bel-7402), and 9.8 ± 1.4 μM (against CT-26). The chick chorioallantoic membrane assay revealed significant anti-angiogenic potential of compound 7x. Molecular imprinting studies suggested the anti-angiogenic effect of compound 7x might be attributed to inhibition of VEGFR2 kinase. Molecular docking and molecular dynamics further indicate that its activity may be primarily associated with the potential inhibition of VEGFR2. Our research outcomes have provided valuable lead compounds for the development of novel antitumor drugs and have offered beneficial insights for subsequent drug design and optimization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Encouraged by the significantly different toxicities and antibacterial activities of diverse linkers, such as alkyl and aromatic nuclei linkers, and the unique structure of phloroglucinol, we synthesized a series of tris-quaternary ammonium salt (tris-QAS) antibacterial peptide mimics based on the marketed drug phloroglucinol. Among them, 2f displayed excellent activity against Staphylococcus aureus (MIC = 0.5 μg/mL) and high selectivity (SI > 2560). Surprisingly, the cytotoxicity of 2f (CC 50 = 152.7 μg/mL) was dramatically better than those of alkyl QAS I and hydroquinone QAS II . Additionally, 2f possessed rapid bactericidal capability, was not prone to inducing bacterial resistance, and also exhibited excellent activity against S. aureus biofilms and persistent bacteria. Mechanistic research and transcriptome analysis revealed that 2f can interfere with the normal metabolism of bacterial cells, and it can specifically bind with phosphatidylglycerol to destroy the cell membrane. Importantly, 2f exhibited potent in vivo antibacterial activity in a mouse subcutaneous methicillin-resistant S. aureus (MRSA) infection model.

Since the discovery of antimicrobial agents, the misuse of antibiotics has led to the emergence of bacterial strains resistant to both antibiotics and common disinfectants like quaternary ammonium compounds (QACs). A new class, 'gemini' QACs, which contain two polar heads, has shown promise. Octenidine (OCT), a representative of this group, is effective against resistant microorganisms but has limitations such as low solubility and high cytotoxicity. In this study, we developed 16 novel OCT derivatives. These compounds were subjected to in silico screening to predict their membrane permeation. Testing against nosocomial bacterial strains (G + and G - ) and their biofilms revealed that most compounds were highly effective against G + bacteria, while compounds 7, 8, and 10-12 were effective against G - bacteria. Notably, compounds 6-8 were significantly more effective than OCT and BAC standards across the bacterial panel. Compound 12 stood out due to its low cytotoxicity and broad-spectrum antimicrobial activity, comparable to OCT. It also demonstrated impressive antifungal activity. Compound 1 was highly selective to fungi and four times more effective than OCT without its cytotoxicity. Several compounds, including 4, 6, 8, 9, 10, and 12, showed strong virucidal activity against murine cytomegalovirus and herpes simplex virus 1. In conclusion, these gemini QACs, especially compound 12, offer a promising alternative to current disinfectants, addressing emerging resistances with their enhanced antimicrobial, antifungal, and virucidal properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jan Marek reports financial support was provided by Ministry of Health of the Czech Republic. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

With increasing health awareness of the pathogenic effects of disease-causing microorganisms, interest in and use (of medical textiles, disinfectants in medical devices, etc.) of antimicrobial substances have increased in various applications, such as medical textiles and disinfectants (alcohol-based and nonalcoholic), in medical devices There are several concerns with alcohol-based disinfectants, such as surface deformation of medical devices due to high alcohol content and damage to skin tissue caused by lipid and protein denaturation of cell membranes. Quaternary ammonium compounds (quats) were preferred because they have the potential to prepare water-based disinfectants. In this study, novel (3-chloropropyl)triethoxysilane (CPTMO) and (3-chloropropyl)triethoxysilane (CPTEO) based quaternary ammonium silane compounds (silane-quats) were developed using quats with carbon chain lengths of C12, C14, C16 and C18. Titration (ASTM D2074) was used to calculate the yield of the synthesis and the structures of the products were characterised by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy ( 13 C NMR, 1 H NMR) and gas chromatography-mass spectrometry (GC-MS).The in vitro antimicrobial activity of the synthesized samples was evaluated against Gram-positive (Staphylococcus aureus (S. aureus), Enterococcus hirae (E. hirae)) and Gram-negative (Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa)) bacteria and fungi (Candida albicans (C. albicans), Aspergillus brasiliensis (A. brasiliensis)) using the minimum inhibitory concentration (MIC) test. According to MIC tests, the silane-quats with the highest antimicrobial effects were dimethylhexadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (SQ3), which had an MIC of < 16 μg/ml (ppm) against E. coli, S. aureus, E. hirae, C. albicans, and A. brasiliensis and 32 μg/ml against P. aeruginosa. The MIC test results also showed antimicrobial activity at least 2 times greater than that of the commercially available disinfectant benzalkonium chloride (BAC). Findings suggest that SQ3 (C16) holds promise as an effective medical disinfectant, presenting a novel approach to combating microbial infections in healthcare settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Quaternary ammonium compounds have served as a first line of protection for human health as surface disinfectants and sanitizers for nearly a century. However, increasing levels of bacterial resistance have spurred the development of novel QAC architectures. In light of the observed reduction in eukaryotic cell toxicity when the alkyl chains on QACs are shorter in nature (≤10 C), we prepared 47 QAC architectures that bear multiple short alkyl chains appended to up to three cationic groups, thus rendering them "bushy-tailed" multiQACs. Antibacterial activity was strong (often ~1-4 μM) in a varied set of bushy-tailed architectures, though observed therapeutic indices were not significantly improved over QAC structures bearing fewer and longer alkyl chains., (© 2024 Wiley-VCH GmbH.)

In this study, three types of dodecyl chitosan quaternary ammonium salts, each with different spacer groups were synthesized. These chitosan derivatives are N',N'-dimethyl-N'-dodecyl-ammonium chloride-N-amino-acetyl chitosan (DMDAC), N'-dodecyl-N-isonicotinyl chitosan chloride (DINCC) and N',N'-dimethyl-N'-dodecyl-ammonium chloride-N-benzoyl chitosan (DMDBC). The synthesized products were characterized using Fourier transform infrared spectrometers, nuclear magnetic resonance, thermogravimetric analysis, and elemental analysis. The antibacterial and antibiofilm activities against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were investigated. The experimental results indicated that the introduction of hydrophobic groups of spacer groups could enhance the antibacterial and antibiofilm activities of the chitosan derivatives. The antibacterial rates of the chitosan derivatives were over 90 % for both E. coli and S. aureus at a concentration of 0.5 mg/mL. The chitosan derivatives removed >50 % of the mature biofilm of E. coli and over 90 % of the mature biofilm of S. aureus at a concentration of 2.5 mg/mL. Further, the synthesized chitosan derivatives were determined to be non-toxic to L929 cells. Among them, DMDBC exhibited the most promising overall performance and show potential for wide-ranging applications in food preservation, disinfectants, medical, and other fields., Competing Interests: Declaration of competing interest We declare that we have no financial or personal relationships with any individuals or organizations that could inappropriately influence our work. We have no professional or personal interest in any product, service, or company that could be seen as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dental caries (DC) is one of the most common oral diseases and is mainly caused by Streptococcus mutans ( S. mutans ). The use of antibiotics against S. mutans usually has side effects, including developing resistance. N-2-Hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC), a natural product, has great potential utility in antibacterial agents owing to its low toxicity and good biocompatibility. Thus, the purpose of the present study was to explore the antimicrobial activity of N-2-HACC against S. mutans through the permeability of the cell wall, integrity of cell membrane, protein and nucleic acid synthesis, respiratory metabolism, and biofilm formation. Our results confirmed that the MIC of N-2-HACC against S. mutans was 0.625 mg/mL with a 90.01 ± 1.54% inhibition rate. SEM observed the formation of cavities on the surface of S. mutans after 12 h N-2-HACC treatment. The level of alkaline phosphatase (AKP) activity was higher in the N-2-HACC treatment group than in the control group, indicating that N-2-HACC can improve the permeability of the cell wall. Also, N-2-HACC treatment can destroy the cell membrane of S. mutans by increasing conductivity and absorbance at 260 nm, decreasing cell metabolic activity, and enhancing the fluorescence at 488 nm. Respiratory metabolism revealed that the activities of the Na + -K + -ATP enzyme, pyruvate kinase (PK), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) were decreased after N-2-HACC treatment, revealing that N-2-HACC can inhibit glycolysis and the tricarboxylic acid cycle (TCA cycle) of S. mutans . Moreover, N-2-HACC can also decrease the contents of the nucleic acid and solution protein of S. mutans , interfere with biofilm formation, and decrease the mRNA expression level of biofilm formation-related genes. Therefore, these results verify that N-2-HACC has strong antibacterial activity against S. mutans , acting via cell membrane integrity damage, increasing the permeability of cell walls, interfering with bacterial protein and nucleic acid synthesis, perturbing glycolysis and the TCA cycle, and inhibiting biofilm formation. It is suggested that N-2-HACC may represent a new potential synthetically modified antibacterial material against S. mutans .

Quaternary ammonium compound (QAC) disinfectants represent one of our first lines of defense against pathogens. Their inhibitory and bactericidal activities are usually tested through minimum inhibitory concentration (MIC) and time-kill assays, but these assays can become cumbersome when screening many compounds. We investigated how the dynamic surface tension (DST) measurements of QACs correlate with these antimicrobial activities by testing a panel of potent and structurally varied QACs against the gram-positive Staphylococcus aureus and the gram-negative Pseudomonas aeruginosa. We found that DST values correlated well with bactericidal activity in real-world disinfection conditions but not with MIC values. Moreover, no correlation between these two antimicrobial activities of QACs (bactericidal and inhibition) was observed. In addition, we observed that the bactericidal activity of our QAC panel against the gram-negative P. aeruginosa was severely affected in the presence of hard water. Interestingly, we found that the counterion of the QAC affects the killing of bacteria in these conditions, a phenomenon not observed in most MIC assessments. Moreover, some of our best-in-class QACs show enhanced bactericidal activity when combined with a commercially available QAC. In conclusion, we determined that an intrinsic physical property of QACs (DST) can be used as a technique to screen for bactericidal activity of QACs in conditions that mimic real-world disinfection conditions., (© 2024 Wiley-VCH GmbH.)

Quaternary ammonium salts (QAS) are widely used in medicine, industry and agriculture as disinfectants, biocides, and fungicides. QAS have the ability to coat various surfaces, prevent adhesion of microorganisms to them and inhibit the formation of biofilm. A group of surfactants derived from benzoic acid with different chemical structures was tested: monomeric QAS with different alkyl chain lengths (C 12 , C 14 , C 16 ), gemini QAS containing 12-carbon alkyl chains and linkers of various lengths (3,4,6 methylene groups), as well as multifunctional QAS. Among the tested surfactants, monomeric QAS showed the highest bactericidal and fungicidal activity. All three groups of tested compounds inhibited the filamentation of C. albicans. The best antimicrobial activity was demonstrated by the monomeric surfactant C 12 AA, while the multifunctional equivalent (2xC 12 AA) was characterized by good anti-adhesive activity. All tested compounds are non-mutagenic and cause low hemolysis of sheep erythrocytes. Multifunctional and gemini surfactants are also non-toxic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Newly synthesized gemini quaternary ammonium salts (QAS) with different counterions (bromide, hydrogen chloride, methylcarbonate, acetate, lactate), chain lengths (C12, C14, C16) and methylene linker (3xCH 2 ) were tested. Dihydrochlorides and dibromides with 12 carbon atoms in hydrophobic chains were characterized by the highest biological activity against planktonic forms of yeast and yeast-like fungi. The tested gemini surfactants also inhibited the production of filaments by C. albicans. Moreover, they reduced the adhesion of C. albicans cells to the surfaces of stainless steel, silicone and glass, and slightly to polystyrene. In particular, the gemini compounds with 16-carbon alkyl chains were most effective against biofilms. It was also found that the tested surfactants were not cytotoxic to yeast cells. Moreover, dimethylcarbonate (2xC 12 MeCO 3 G 3 ) did not cause hemolysis of sheep erythrocytes. Dihydrochlorides, dilactate and diacetate showed no mutagenic potential., (© 2024. The Author(s).)

Cationic biocides play a crucial role in the disinfection of domestic and healthcare surfaces. Due to the rise of bacterial resistance towards common cationic disinfectants like quaternary ammonium compounds (QACs), the development of novel actives is necessary for effective infection prevention and control. Toward this end, a series of 15 chimeric biscationic amphiphilic compounds, bearing both ammonium and phosphonium residues, were prepared to probe the structure and efficacy of mixed cationic ammonium-phosphonium structures. Compounds were obtained in two steps and good yields, with straightforward and chromatography-free purifications. Antibacterial activity evaluation of these compounds against a panel of seven bacterial strains, including two MRSA strains as well as opportunistic pathogen A. baumannii, were encouraging, as low micromolar inhibitory activity was observed for multiple structures. Alkyl chain length on the ammonium group was, as expected, a major determinant of bioactivity. In addition, high therapeutic indexes (up to 125-fold) for triphenyl phosphonium-bearing amphiphiles were observed when comparing antimicrobial activity to mammalian cell lysis activity., (© 2024 Wiley-VCH GmbH.)

Herein, we present an innovative synthetic approach for producing a diverse set of biobased oligomers. This method begins with olive oil and employs a wide variety of commercially available amino acids (AAs) as bio-organocatalysts, in addition to tetrabutylammonium iodide (TBAI) as a cocatalyst, to synthesize various biobased oligomers. These biobased oligomers were strategically prepared starting from epoxidized olive oil (EOO) and a variety of cyclic anhydrides (phthalic, PA; maleic, MA; succinic, SA; and glutaric, GA). Among the amino acids tested as bio-organocatalysts, L-glutamic acid (L-Glu) showed the best performance for the synthesis of both poly(EOO- co -PA) and poly(EOO- co -MA), exhibiting 100% conversion at 80 °C in 2 hours, whereas the formation of poly(EOO- co -SA) and poly(EOO- co -GA) required more extreme reaction conditions (72 hours under toluene reflux conditions). Likewise, we have succeeded in obtaining the trans isomer exclusively for the MA based-oligomer within the same synthetic framework. The obtained oligomers were extensively characterized using techniques including NMR, FT-IR, GPC and TGA. A series of computational simulations based on density functional theory (DFT) and post-Hartree Fock (post-HF) methods were performed to corroborate our experimental findings and to obtain an understanding of the reaction mechanisms.

In this study, a library of 3,7-di(hetero)aryl-substituted 10-(3-trimethylammoniumpropyl)10 H -phenothiazine salts is prepared. These title compounds and their precursors are reversible redox systems with tunable potentials. The Hammett correlation gives a very good correlation of the first oxidation potentials with σ p parameters. Furthermore, the title compounds and their precursors are blue to green-blue emissive. Screening of the salts reveals for some derivatives a distinct inhibition of several pathogenic bacterial strains ( Mycobacterium tuberculosis , Staphylococcus aureus , Escherichia coli , Aconetobacter baumannii , and Klebsiella pneumoniae ) in the lower micromolar range.

This review provides a comprehensive overview of recent advancements in the design and synthesis of biologically active quaternary ammonium compounds (QACs). The covered scope extends beyond commonly reviewed antimicrobial derivatives to include synthetic agents with antifungal, anticancer, and antiviral properties. Additionally, this review highlights examples of quaternary ammonium compounds exhibiting activity against protozoa and herbicidal effects, as well as analgesic and anesthetic derivatives. The article also embraces the quaternary-ammonium-containing cholinesterase inhibitors and muscle relaxants. QACs, marked by their inherent permanent charge, also find widespread usage across diverse domains such as fabric softeners, hair conditioners, detergents, and disinfectants. The effectiveness of QACs hinges greatly on finding the right equilibrium between hydrophilicity and lipophilicity. The ideal length of the alkyl chain varies according to the unique structure of each QAC and its biological settings. It is expected that this review will provide comprehensive data for medicinal and industrial chemists to design and develop novel QAC-based products.

The new chalcogenylation of phosphines using n Bu 4 N‧XCN (X = S, Se) is described. The reaction in 1,2-dichloroethane at 120 °C provided the corresponding phosphine sulfides in good to high yields. The protocol could be extended to the synthesis of phosphinic acid derivatives as well as sulfurization of poly(styrene-co-4-styryldiphenylphosphine).

A series of quaternary diammonium salts derivatives of 1,4:3,6-dianhydro-l-iditol were synthesized, using isommanide (1,4:3,6-dianhydro-d-mannitol) as a starting material. Both aromatic (pyridine, 4-( N , N -dimethylamino)pyridine (DMAP), (3-carboxamide)pyridine; N -methylimidazole) and aliphatic (trimethylamine, N , N -dimethylhexylamine, N , N -dimethyloctylamine, N , N -dimethyldecylamine) amines were used, giving eight gemini quaternary ammonium salts (QAS). All salts were tested for their antimicrobial activity against yeasts, Candida albicans and Candida glabrata , as well as bacterial Staphylococcus aureus and Escherichia coli reference strains. Moreover, antibacterial activity against 20 isolates of S. aureus collected from patients with skin and soft tissue infections ( n = 8) and strains derived from subclinical bovine mastitis milk samples ( n = 12) were evaluated. Two QAS with octyl and decyl residues exhibited antimicrobial activity, whereas those with two decyl residues proved to be the most active against the tested pathogens, with MIC of 16-32, 32, and 8 µg/mL for yeast, E. coli, and S. aureus reference and clinical strains, respectively. Only QAS with decyl residues proved to be cytotoxic in MTT assay against human keratinocytes (HaCaT), IC 50 12.8 ± 1.2 μg/mL. Ames test was used to assess the mutagenic potential of QAS, and none of them showed mutagenic activity in the concentration range 4-2000 µg/plate.

One of the concerns today's societies face is the development of resistant pathogenic microorganisms. The need to tackle this problem has driven the development of innovative antimicrobial materials capable of killing or inhibiting the growth of microorganisms. The present study investigates the dependence of the antimicrobial activity and solubility properties on the hydrophilicity/hydrophobicity ratio of antimicrobial coatings based on quaternary ammonium compounds. In this line, suitable hydrophilic and hydrophobic structural units were selected for synthesizing the antimicrobial copolymers poly(4-vinylbenzyl dimethyldodecylammonium chloride-co-acrylic acid), P(VBCDDA-co-AA20) and poly(dodecyltrimethylammonium 4-styrene sulfonate-co-glycidyl methacrylate), P(SSAmC 12 -co-GMA20), bearing an alkyl chain of 12 carbons either through covalent bonding or through electrostatic interaction. The cross-linking reaction of the carboxylic group of acrylic acid (AA) with the epoxide group of glycidyl methacrylate (GMA) of these two series of reactive antimicrobial copolymers was explored in blends, obtained through solution casting after curing at various temperatures. The release of the final products in pure water and NaCl 1 M solutions (as analyzed by gravimetry and total organic carbon, TOC/total nitrogen, TN analyses), could be controlled by the coating composition. The cross-linked polymeric membranes of composition 60/40 w / w % ratios led to 97.8 and 99.7% mortality for Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ), respectively, whereas the coating 20/80 w / w % resulted in 96.6 and 99.8% cell reduction. Despite the decrease in hydrophobicity (from a 16- to a 12-carbon alkyl chain), the new materials maintained the killing efficacy, while at the same time resulting in increased release to the aqueous solution.

A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes 3a - h and related quaternary ammonium salts 4a - h were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series 3 and 4 to be potent cytotoxins with submicromolar CC 50 values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure-activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, 3a - h are cytotoxic towards a number of leukemic and colon cancer cells. 4b , c lowered the mitochondrial membrane potential in CEM cells, and 4d induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely 3c , d and 4c-e , were identified as lead molecules that have drug-like properties.

Bio-based ionic liquids (ILs) are being increasingly sought after, as they are more sustainable and eco-friendly. Purines are the most widely distributed, naturally occurring N -heterocycles, but their low water-solubility limits their application. In this work, four purines (theobromine, theophylline, xanthine, and uric acid) were combined with the cation tetrabutylammonium to synthesize bio-based ILs. The physico-chemical properties of the purine-based ILs were characterized, including their melting and decomposition temperatures and water-solubility. The ecotoxicity against the microalgae Raphidocelis subcapitata was also determined. The ILs show good thermal stability (>457 K) and an aqueous solubility enhancement ranging from 53- to 870-fold, in comparison to their respective purine percursors, unlocking new prospects for their application where aqueous solutions are demanded. The ecotoxicity of these ILs seems to be dominated by the cation, and it is similar to chloride-based IL, emphasizing that the use of natural anions does not necessarily translate to more benign ILs. The application of the novel ILs in the formation of aqueous biphasic systems (ABS), and as solubility enhancers, was also evaluated. The ILs were able to form ABS with sodium sulfate and tripotassium citrate salts. The development of thermoresponsive ABS, using sodium sulfate as a salting-out agent, was accomplished, with the ILs having different thermosensitivities. In addition, the purine-based ILs acted as solubility enhancers of ferulic acid in aqueous solution.

Novel eco-friendly and green dimethyldiallylammonium chloride (DMDAAC) grafted chitosan/genipin/cellulose hydrogel beads (CCBG-g-PDMDAAC), were fabricated as selective adsorbents for anionic dyes. The physical and chemical structural changes of the prepared hydrogels were evaluated by FTIR, XRD, SEM and TG-DSC analysis. Results showed CCBG-g-PDMDAAC efficiently and selectively adsorb anionic dyes (Reactive Red 195-RR195 and Methyl orange-MO) from mixture of dye solutions. Endowed chitosan-based hydrogels the advantage of acid insolubility and good adsorption. RR195 and MO adsorption process were described better with pseudo-second-order kinetic model and Langmuir isotherm model with a maximum adsorption capacity of 1333.52 and 190.48 mg/g, respectively, indicating that monolayer chemisorption controlled the sorption process. Moreover, the hydrogels exhibited nice reusability and against S. aureus and E. coli. The hydrogels are promising for the potential application in wastewater treatment and antibacterial simultaneously., (Copyright © 2021. Published by Elsevier B.V.)

Herein we report the synthesis and microbiological evaluation of novel phenyl based bis-quaternary ammonium compounds (bis-QACs). Using a simple 2-step synthetic route from dibromo- and dihydroxybenzenes, we obtained a structurally diverse broad panel of bis-QACs with topologically distinct bridging connections between pyridinium heads. Selected analogs possessed potent broad-spectrum biocidal activity against both bacterial and fungal pathogens: methicillin-resistant Staphylococcus aureus (ATCC 43300); Escherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 700603), Acinetobacter baumannii (ATCC 19606), Pseudomonas aeruginosa (ATCC 27853), Candida albicans (ATCC 90028), Cryptococcus neoformans var. grubii (ATCC 208821). Promising compounds displayed minimum inhibitory concentrations (MIC) values ≤0.25 μg/mL alongside improved cytotoxicity and hemolytic profiles compared to modern antiseptics. Thus, synthesized bis-QACs represent a promising class of biocides with the potential to replace existing household sanitizers., (© 2021 Wiley-VCH GmbH.)

The development of organic polymer materials for disinfection and sterilization is thought of as one of the most promising avenues to solve the growth and spread of harmful microorganisms. Here, a series of linear polyisocyanide quaternary ammonium salts (L-PQASs) with different structures and chain lengths were designed and synthesized by polymerization of phenyl isocyanide monomer containing a 4-chloro-1-butyl side chain followed by quaternary amination salinization. The resultant compounds were characterized by 1 H NMR and FT-IR. The antibacterial activity of L-PQASs with different structures and chain lengths against Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ) was evaluated by determining the minimum inhibitory concentrations (MICs). The L-POcQAS-M 50 has the strongest antimicrobial activity with MICs of 27 μg/mL against E. coli and 32 μg/mL against S. aureus. When the L-PQASs had the same polymerization degree, the order of the antibacterial activity of the L-PQASs was L-POcQAS-M n > L-PBuQAS-M n > L-PBnQAS-M n > L-PDBQAS-M n (linear, polyisocyanide quaternary ammonium salt, monomer, n = 50,100). However, when L-PQASs had the same side chain, the antibacterial activity reduced with the increase of the molecular weight of the main chain. These results demonstrated that the antibacterial activity of L-PQASs was dependent on the structure of the main chain and the length of the side chain. In addition, we also found that the L-POcQAS-M 50 had a significant killing effect on MK-28 gastric cancer cells.

Control of molecular chirality is a fundamental challenge in organic synthesis. Whereas methods to construct carbon stereocentres enantioselectively are well established, routes to synthesize enriched heteroatomic stereocentres have garnered less attention 1-5 . Of those atoms commonly present in organic molecules, nitrogen is the most difficult to control stereochemically. Although a limited number of resolution processes have been demonstrated 6-8 , no general methodology exists to enantioselectively prepare a nitrogen stereocentre. Here we show that control of the chirality of ammonium cations is easily achieved through a supramolecular recognition process. By combining enantioselective ammonium recognition mediated by 1,1'-bi-2-naphthol scaffolds with conditions that allow the nitrogen stereocentre to racemize, chiral ammonium cations can be produced in excellent yields and selectivities. Mechanistic investigations demonstrate that, through a combination of solution and solid-phase recognition, a thermodynamically driven adductive crystallization process is responsible for the observed selectivity. Distinct from processes based on dynamic and kinetic resolution, which are under kinetic control, this allows for increased selectivity over time by a self-corrective process. The importance of nitrogen stereocentres can be revealed through a stereoselective supramolecular recognition, which is not possible with naturally occurring pseudoenantiomeric Cinchona alkaloids. With practical access to the enantiomeric forms of ammonium cations, this previously ignored stereocentre is now available to be explored., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

An orthogonal strategy was utilized for synthesizing a novel water-soluble pillar[5]arene ( m -TPEWP5 ) with tetraphenylethene-functionalized on the bridged methylene group ( meso -position) of the pillararene skeleton. The obtained macrocycle exhibit both the aggregation-induced emission (AIE) effect and interesting host-guest property. Moreover, it can be made to bind with a tailor-made camptothecin-based prodrug guest ( DNS-G ) to form AIE-nanoparticles based on host-guest interaction and the fluorescence resonance energy transfer process for fabricating a drug delivery system. This novel type of water-soluble AIE-active macrocycle can serve as a potential fluorescent material for cancer diagnosis and therapy. In addition, the present orthogonal strategy for designing meso -functionalized aromatic macrocycles may pave a new avenue for creating novel supramolecular structures and functional materials.

Aerobic alcohol oxidations catalyzed by transition metal salts and aminoxyls are prominent examples of cooperative catalysis. Cu/aminoxyl catalysts have been studied previously and feature "integrated cooperativity", in which Cu II and the aminoxyl participate together to mediate alcohol oxidation. Here we investigate a complementary Fe/aminoxyl catalyst system and provide evidence for "serial cooperativity", involving a redox cascade wherein the alcohol is oxidized by an in situ-generated oxoammonium species, which is directly detected in the catalytic reaction mixture by cyclic step chronoamperometry. The mechanistic difference between the Cu- and Fe-based catalysts arises from the use iron(III) nitrate, which initiates a NO x -based redox cycle for oxidation of aminoxyl/hydroxylamine to oxoammonium. The different mechanisms for the Cu- and Fe-based catalyst systems are manifested in different alcohol oxidation chemoselectivity and functional group compatibility.

Phenanthroindolizidines, such as antofine and tylophorine, are a family of natural alkaloids isolated from different species of Asclepiadaceas. They are characterized by interesting biological activities, such as pronounced cytotoxicity against different human cancerous cell lines, including multidrug-resistant examples. Nonetheless, these derivatives are associated with severe neurotoxicity and loss of in vivo activity due to the highly lipophilic nature of the alkaloids. Here, we describe the development of highly polar prodrugs of antofine and tylophorine as hypoxia-targeted prodrugs. The developed quaternary ammonium salts of phenanthroindolizidines showed high chemical and metabolic stability and are predicted to have no penetration through the blood-brain barrier. The designed prodrugs displayed decreased cytotoxicity when tested under normoxic conditions. However, their cytotoxic activity considerably increased when tested under hypoxic conditions.

The synthesis of environmentally friendly antimicrobial polymeric coatings, especially in the case of aquaculture, that inhibit the growth of bio-deposits is a very important issue that will contribute to the cost reduction of nets' cleaning process as well as the protection of the submarine wealth from the biostatic substances used so far. In the present work, the antimicrobial polymers P(SSAmC 16 -co-VBCHAMx) and the terpolymer P(SSAmC 16 w-co-VBCHAMx-co-GMAy) were synthesized, bearing quaternary ammonium compounds, electrostatically bound and covalently attached at the same polymer chain. The combination of the two types is of particular importance, as it can provide effective antimicrobial polymeric materials with self-polishing capabilities as a result of the released nature of the antimicrobial, in combination with the permanent local action of the immobilized species. The cross-linking reaction of the terpolymer P(SSAmC 16 w-co-VBCHAMx-co-GMAy) with the homopolymer polyacrylic acid (PAA) was tested at 120 °C in terms of the equivalent ratio between epoxy and carboxyl groups. The synthesized polymers were further used for the coating of aquaculture nets and tested in terms of antifouling efficiency in lab and scale-up conditions. Uncoated nets were also used in all applications for comparison reasons. The coated nets performed efficiently for 35 days in lab-scale and 66 days in scale-up conditions, showing a high antifouling activity in both fields compared to the uncoated nets.

Recent advances in the development of quaternary ammonium compounds (QACs) have focused on new structural motifs to increase bioactivity, but significantly less studied has been the change from ammonium- to sulfonium-based disinfectants. Herein, we report the synthesis of structurally analogous series of quaternary ammonium and trivalent sulfonium compounds (TSCs). The bioactivity profiles of these compounds generally mirror each other, and the antibacterial activity of sulfonium-based THT-18 was found to be comparable to the commercial disinfectant, BAC. The development of these compounds presents a new avenue for further study of disinfectants to combat the growing threat of bacterial resistance., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The prevention and treatment of microorganism contamination on substrate surfaces have recently generated significant concern of scientists. In this paper, a novel diblock copolymer containing antibacterial quaternary ammonium groups as pendant groups, poly(3-(methacryloylamino) propyltrimethyl ammonium chloride)-b-poly(styrene) (PMS), was synthesized by interfacial polymerization. Also, PMS anisotropic particles (APs) could be successfully obtained based on different assembly behaviors by adjusting the ratios of monomers and the toluene/styrene (Tol/St). Moreover, silver loaded chitosan (Ag@CS) and PMS APs were combined to prepare natural/synthetic polymer antibacterial materials with dual-active centers (Ag@CS/PMS-4 APs), aiming to expand the application of carbohydrate polymers and improve the antibacterial activity of composite materials. Remarkably, the resulting series of PMS particles, especially worm-like PMS-4 APs, and Ag@CS/PMS-4 APs composite film ((Ag@CS/PMS-4 APs)-F) exhibited excellent antibacterial properties, which can be employed as interface materials to prevent the transmission of infectious diseases caused by microorganism contamination., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Commercial disinfectants are routinely used to decontaminate surfaces where microbes are expected and unwelcome. Several disinfectants contain quaternary ammonium salts, or "quats", all being derived from ammonium. Quaternary alkyl dimethyl benzyl ammonium chloride or bromide disinfectants are widely available. These compounds are effective in reducing or eliminating bacteria on contaminated nonporous surfaces. A unique benzyl derived boronium salt with strong detergent action has been developed. It demonstrated 4-8X greater antibacterial activity against 3 different bacteria when compared to an equal concentration of a commercial quant disinfectant solution containing alkyl dimethyl benzyl ammonium chloride and alkyl dimethyl ethylbenzyl ammonium chloride. Antibacterial effectiveness of each agent was determined by the minimum inhibitory concentration (MIC) method., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Novel quaternary ammonium surfactants (QUATs) derived from phenylalaninyl-proline dipeptide with chain length C 12 and C 14 were synthesised as potential active ingredients to be used in body cleansing formulations. The physicochemical properties and biological activities of the QUATs were determined in both single and in mixed surfactant system with either the conventional anionic surfactant sodium dodecyl sulphate (SDS) or sodium N-dodecyl prolinate. The C 12 QUAT derivative showed antagonistic behaviour in both SDS and sodium N-dodecyl prolinate mixed surfactant system. Comparing the mixed system of the C 12 QUAT with SDS and sodium N-dodecyl prolinate, it was found that the latter displayed better antibacterial activity together with the lower ocular irritation. The C 12 QUAT-sodium N-dodecyl prolinate mixture were non cytotoxic at a concentration corresponding to its MIC value, showing that the mixture was selective towards bacterial cells rather than mammalian cell lines. Diffusion measurements showed that the sodium N-dodecyl prolinate surfactant consisted of 26 molecules per micelle in water but only 3 molecules per micelle in DMSO/water (1:1). On the other hand, C 12 QUAT did not form a micelle in DMSO/Water. Membrane permeability studies of the C 12 QUAT and sodium N-dodecyl prolinate showed that these surfactants are capable to penetrate into deeper skin layers to exert their antibacterial and cleansing action and hence can be used as a promising candidate as active ingredients in body wash formulations., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A diverse series of 43 novel "soft antimicrobials" based on quaternary ammonium pyridoxine derivatives which include six-membered acetals and ketals of pyridoxine bound via cleavable linker moieties (amide, ester) with a fragment of fatty carboxylic acid was designed. Nine compounds exhibited in vitro promising antibacterial activity against Gram-positive and Gram-negative bacterial strains with MIC values comparable with reference antiseptics miramistin, benzalkonium chloride and chlorohexidine. On various clinical isolates, the lead compounds 6i and 12a exhibited antibacterial activity comparable with that of benzalkonium chloride while higher than that of miramistin. Moreover, 6i and 12a were able to kill bacteria embedded into the matrix of mono- and dual species biofilms. The treatment of bacterial cells by either 6i and 12a lead to fast depolarization of the membrane suggesting that the membrane is an apparent molecular target of compounds. 6i and 12a were non mutagenic neither in SOS-chromotest nor in Ames test and non-toxic in vivo at acute oral (LD 50  > 2000 mg/kg) and cutaneous administration (LD 50  > 2500 mg/kg) on mice. Taken together, our data allow suggesting described active compounds as promising starting point for the new antibacterial agents development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Giosgenin is a naturally steroidal saponin exhibiting a variety of biological activities including antitumor ones. A series of novel diosgenyl quaternary ammonium derivatives were designed and synthesized to develop potential anti-tumor agents in our research. All novel derivatives were characterized by 1 H NMR, 13 C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. The human cancer cell lines were A549 (Human lung cancer cell), H1975 (Human lung adenocarcinoma cell), A431 (Human skin squamous cell carcinoma), HCT-116 (Human colorectal adenocarcinoma cell), Aspc-1 (Human metastatic pancreatic cancer cell), Ramos (Human B lymphoma cell), HBE (Human bronchial epithelioid cell) and LO2 (Human normal hepatocyte)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Octyltrimethylammonium tetrathiotungstate salt (ATT-C8) was synthesized and its ability to chelate copper was evaluated. The biological and toxic aspects were evaluated by in vitro and in vivo assays, using bovine aorta endothelial cells (BAEC) and zebrafish (Danio rerio) embryos. The obtained results suggest that ATT-C8 has better biocompatibility, showing a significantly lower lethal concentration 50 (LC 50 ) value in comparison to ammonium tetrathiotungstate (ATT). Zebrafish embryos assay results indicate that both tetrathiotungstate salts at the studied concentrations increase the hatching time. Even more, an in vivo assay showed that synthesized materials behave as copper antagonists and have the ability to inhibit its toxicological effects. Also, both materials were found to be active for the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The characterization of the materials was carried out using the following spectroscopic techniques: Ultraviolet-Visible (UV-Vis), Fourier Transform Infrared (FTIR) and proton nuclear magnetic resonance ( 1 H-NRM).

Graphene oxide (GO) crosslinked nanocomposites hydrogels (NCH) of chitosan (CS) and carboxymethyl cellulose (CMC) were synthesized and the feasibility of its application as a versatile adsorbent for the remediation of cationic (methylene blue, MB) as well as anionic (methyl orange, MO) dyes contaminated wastewater was explored. Initially, GO was functionalized with vinyltriethoxysilane which was subsequently used as a chemical crosslinker to synthesize the NCH of CS and CMC (CS/CMC-NCH) with the polymeric mixture of diallyldimethylammonium chloride and 2-acrylamido-2-methyl-1-propanesulfonic acid. About 99% dye was adsorbed from 50 mg/L dye solution of MB dye with 0.4 g/L of CS/CMC-NCH at pH 7, whereas, for MO about 82% dye was adsorbed with 0.6 g/L of CS/CMC-NCH at pH 3. The Adsorption of both dyes is well explained using pseudo-second-order and Langmuir models with the maximum adsorption capacities of 655.98 mg dye /g ads for MB and 404.52 mg dye /g ads for MO. Thermodynamics studies suggested spontaneous and exothermic nature of the adsorption process with values of ΔS < 0 and ΔH > 0. Furthermore, CS/CMC-NCH showed excellent regeneration capacity for continuous twenty cycles of adsorption-desorption. Therefore, the synthesized CS/CMC-NCH is a versatile adsorbent that can treat both anionic and cationic dyes contaminated wastewater., (Copyright © 2020 Elsevier B.V. All rights reserved.)

New 1,3 dibenzyl -tetrahydropyridinylidene ammonium salts have been prepared from unsubstituted or N-benzylated tetrahydropyridinylidene ammonium salts. The antiplasmodial and antitrypanosomal activities as well as their cytotoxic effects were determined using microplate assays. In addition, their activities against two gram positive and two gram negative bacteria strains and a yeast strain were examined. Furthermore, anticancer effects against two cell lines were investigated. Physicochemical parameters were calculated and structure-activity-relationships discussed. One compound showed antiplasmodial activity against a multiresistant strain of Plasmodium falciparum in subnanomolar concentration. Antitrypanosomal activities were detected in low nanomolar concentrations. A single compound was active against grampositive and gramnegative bacteria, as well as yeast. One compound inhibited the growth of a HCT cell line in low concentration., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Controllable drug release is promising for fighting against antimicrobial resistance, which is a critical threat to human health worldwide. Herein, new hyaluronidase-responsive conjugated oligo(thiophene ethynylene) (OTE)-covalently modified hyaluronic acid (OTE-HA) nanoparticles for on-demand release of antimicrobial agents are reported. The synthesis of amphiphilic OTE-HA was carried out by esterification reaction. The resulting macromolecules were self-assembled in water to form nanoparticles, in which the hydrophobic OTE section, as bactericides, formed "cores" and the hydrophilic hyaluronic acid (HA) formed "shells". The OTE-HA nanoparticles avoid bactericide premature leakage and effectively block the dark cytotoxicity of the OTE section, possessing excellent biocompatibility. Using methicillin-resistant Staphylococcus aureus (MRSA) as an example, hyaluronidase, largely secreted by MRSA, can in situ trigger the release of OTE via hydrolyzing OTE-HA nanoparticles into fragments, even disaccharides linked with OTE. Importantly, the OTE section could effectively break cell membranes, leading to bacterial death. The half-maximal inhibitory concentration of the nanoparticles against MRSA is 3.3 μg/mL. The great antibacterial activity of OTE-HA nanoparticles against Gram-positive bacteria Streptococcus pneumoniae further confirms the controllable bactericide delivery mechanism. OTE-HA nanoparticles coated on a surface can also effectively inhibit the growth of bacteria, which holds a remarkable promise in biomedical applications. Therefore, this work provides a favorable strategy of on-demand and in situ drug release for sterilization and defeating antimicrobial resistance.

Quaternary ammonium compounds are widely used as antiseptic and disinfectant. It is been a concern that their widespread use will lead to an increase of environmental problems, therefore the development of biodegradable surfactants is necessary. The present research is aimed at the design of novel amphiphilic molecules with similar properties to those already known but more biodegradable. Based on benzalkonium chloride (BAC), novel carbonate cleavable surfactants (CBAC) were synthesized. The breakable carbonate sites make CBAC compounds more degradable and potentially more biodegradable than their non-cleavable BAC analogues. Natural products such as fatty alcohols (C 8 -C 16 ) and N,N-dimethyl-2-aminoethanol were used as reagents for the synthesis of CBAC8-16. These amphiphilic compounds were characterized in terms of surface properties and antimicrobial activity against Gram-positive and Gram-negative bacteria, yeasts and moulds. The novel surfactants showed similar surface activities in aqueous solutions when compared to BAC. Also, the surface activity/structure relationship revealed that carbonate cleavable surfactants with n-decyl group (CBAC10) showed the same behaviour as non-cleavable BAC. Furthermore, compounds containing n-octyl (CBAC8), n-decyl (CBAC10) and n-dodecyl (CBAC12) group showed strong antimicrobial activities.

Ionic liquids are increasingly used for their superior properties. Four water-immiscible ionic liquids (butyltriethylammonium bis(trifluoromethylsulfonyl)imide, octyltriethylammonium bis(trifluoromethylsulfonyl)imide, dodecyltriethylammonium bis(trifluoromethylsulfonyl)imide, butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) and their water miscible precursors (bromides) were synthesized in a microwave reactor and by conventional heating. The best conditions for microwave-assisted synthesis concerning the yield and the purity of the product are proposed. The heating in the microwave reactor significantly shortened the reaction time. Biocide and ecotoxic effects of synthesized ionic liquids and their precursors were investigated. All tested compounds had at least a little effect on the growth or living of microorganisms (bacteria or mold). The precursor dodecyltriethylammonium bromide was found to be the strongest biocide, but posed a risk to the aquatic environment due to its relatively high EC 50 value in the test with Vibrio fischeri . We assumed that apart from the alkyl chain length, the solubility in water, duration of action, or type of anion can influence the final biocide and ecotoxic effect.

The prevalence of quaternary ammonium compounds (QACs) as common disinfecting agents for the past century has led bacteria to develop resistance to such compounds. Given the alarming increase in resistant strains, new strategies are required to combat this rise in resistance. Recent efforts to probe and combat bacterial resistance have focused on studies of multiQACs. Relatively unexplored, however, have been changes to the primary atom bearing positive charge in these antiseptics. Here we review the current state of the field of both phosphonium and sulfonium amphiphilic antiseptics, both of which hold promise as novel means to address bacterial resistance., (© 2020 Wiley-VCH GmbH.)

Many pathogenic bacteria and microscopic fungi form rigid polymicrobial biofilms this way enhancing their resistant to treatment. A series of novel pyridoxine-based quaternary ammonium derivatives of terbinafine characterized by both antifungal and antibacterial activities was designed. The leading compound named KFU-127 exhibits promising antifungal and antibacterial activities against various bacteria and micromycetes in both planktonic and biofilm-embedded forms demonstrating MIC values comparable with those of conventional antifungals and antimicrobials. Similar to other antiseptics like benzalkonium chloride and miramistin, KFU-127 is considerably toxic for eukaryotic cells that limits is application to topical treatment options. On the other hand, KFU-127 reduces the number of viable biofilm-embedded bacteria and C. albicans by 3 orders of magnitude at concentrations 2-4 times lower than those of reference drugs and successfully eradicates S. aureus-C. albicans mixed biofilms. The mechanism of antimicrobial action of KFU-127 is bimodal including both membrane integrity damage and pyridoxal-dependent enzymes targeting. We expect that this bilateral mechanism would result in lower rates of resistance development in both fungal and bacterial pathogens. Taken together, our data suggest KFU-127 as a new promising broad spectrum topical antimicrobial capable of one-shot targeting of bacterial and fungal-bacterial biofilms., (Copyright © 2020 Elsevier Inc. All rights reserved.)