School of Pharmacy, Queens University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL, UK; Institute for Cancer Research, 123 Old Brompton Road, London, SW7 3RP, UK.
The QUILL Research Centre, School of Chemistry, Queen's University of Belfast, Belfast, BT9 5AG, UK.
Chemosphere. 2021 May;270:129432. doi: 10.1016/j.chemosphere.2020.129432. Epub 2020 Dec 31.
The ability to chemically modify ionic liquids (ILs) has led to an expansion in interest in their use in a diversity of applications, not least as antimicrobials and biocides. Relatively little is known about cytotoxicity mechanisms of ILs in comparison to other biocides currently in widespread use, as well as their practical significance for the ecological environment and human health. Using NCTC 2544 and HaCat human keratinocyte cells, this study aimed to characterize cytotoxicity rates and mechanisms of a range of ILs. Using both lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based cytotoxicity assays, it was confirmed that at biocide-relevant concentrations, ILs with longer alkyl chains exhibited greater biocidal activity than those with shorter alkyl chains, with comparable activity to the commonly used biocides chlorhexidine, benzalkonium chloride and cetylpyridinium chloride, at relevant in-use biocide concentrations. Mode of cell death, measured using fluorescence-activated cell sorting (FACS) and caspase 3/7 activity, determined necrosis to be the primary cytotoxic mechanism at higher concentrations of the biocides stated above, and with ILs [CMIM]Cl and [Cquin]Br, with apoptosis observed at borderline necrotic concentrations. Perhaps most interestingly, modification of anion had a significant effect on cytotoxicity. The use of N[SOCF] as an anion to [CMIM] attenuated cytotoxicity 10-fold in comparison to other anions, suggesting cytotoxicity may also be a tuneable property when using ILs as biocides.
能够对离子液体（ILs）进行化学修饰，使得人们对其在各种应用中的使用产生了兴趣，尤其是作为抗菌剂和杀生剂。与目前广泛使用的其他杀生剂相比，人们对 ILs 的细胞毒性机制知之甚少，以及它们对生态环境和人类健康的实际意义。本研究使用 NCTC 2544 和 HaCat 人角质形成细胞，旨在表征一系列 ILs 的细胞毒性率和机制。使用乳酸脱氢酶（LDH）和 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）基于细胞毒性测定法，证实了在杀生剂相关浓度下，具有较长烷基链的 ILs 比具有较短烷基链的 ILs 表现出更高的杀菌活性，与常用的杀生剂洗必泰、苯扎氯铵和十六烷基氯化吡啶在相关使用杀生剂浓度下的活性相当。通过荧光激活细胞分选（FACS）和 caspase 3/7 活性测量的细胞死亡方式，确定在上述更高浓度的杀生剂作用下，坏死是主要的细胞毒性机制，而对于 ILs [CMIM]Cl 和 [Cquin]Br，在边界坏死浓度下观察到凋亡。也许最有趣的是，阴离子的修饰对细胞毒性有显著影响。与其他阴离子相比，将 N[SOCF]用作阴离子修饰 [CMIM]，可使细胞毒性降低 10 倍，这表明当将 ILs 用作杀生剂时，细胞毒性也可能是一个可调节的特性。
