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Natamycin (synonym pimaricin) is an antimycotic agent of the polyene macrolide class of antimicrobials used as a surface treatment of cheeses and dried sausages. Natamycin exerts its fungicidal activity by preventing the growth of fungi and germination of fungal spores through binding to ergosterol located in fungal cellular membranes. At its Fifty-first Session, the CCFA requested a re-evaluation of the safety of natamycin including any data on “(i) promoting antimicrobial resistance, as well as speeding up virulence and pathogenic potential of food-borne human pathogens; and (ii) unbalancing the immunity and other bodily functions due to effects on gastrointestinal microflora; dietary intake and specifications” (174). Natamycin was evaluated by the previous Committee at its Twelfth, Twentieth, Fifty-seventh and Sixty-seventh meetings (103,175–177). At the Twelfth meeting, the Committee established a conditional ADI18 of 0–0.25 mg/kg bw. The conditional ADI was converted to an ADI of 0–0.3 mg/kg bw at the Twentieth meeting based on observations of gastrointestinal effects in humans (176). At the Fifty-seventh meeting, the Committee confirmed the previously established ADI of 0–0.3 mg/kg bw for natamycin (177). The Joint FAO/WHO Meeting on Pesticide Residues (JMPR) evaluated natamycin in 2017 and concluded that the available evidence was inadequate to draw a conclusion on the genotoxicity and carcinogenic potential of natamycin (178). JMPR did not establish an ADI for natamycin because of the inadequate database available to the 2017 meeting. The sponsor submitted studies investigating the toxicity and microbiological effects of natamycin. Comprehensive literature searches were also undertaken on the toxicological, antimicrobial resistance and dietary exposure aspects of this assessment in databases such as PubMed and Web of Science from 2001 to 2024, using keywords including “natamycin”, “pimaricin”, “metabolite”, “toxicity”, “polyene”, “

Modified silver nanoparticles with a self‐assembled disulfide functionalized 2,2'‐bipyridine (L1 and L2) monolayer, and the corresponding rhenium complex [Re(L2)(CO)3Br] are shown to provide a method to position the nanoparticles at a water/dichloromethane interface forming a lustrous metal‐like‐liquid film (MeLLF) with a unique SERS response. The film formed using L2 showed divergent behaviour in the presence of a range of metal ions whilst bound to the surface. [Re(L)(CO)3Br] (where L=2,2'‐bipyridine, L1 and L2) in solution demonstrates a selective interaction with Hg2+, observed by UV‐vis, emission and 1H NMR spectroscopy, attributed to abstraction of the bromide. This interaction was demonstrated by subtle changes in the characteristic Raman Re‐CO stretch at 510 cm−1 both with the MeLLF, and when the film is immobilized in a PVA surface‐exposed‐nano‐sheet (SENS). The work provides proof of concept that the organometallic complexes can be employed as “labels” to generate SERS‐active nanoparticle films that possess detection capabilities.

Modified silver nanoparticles with a self-assembled disulfide functionalized 2,2´-bipyridine (L1 and L2) monolayer, and the corresponding rhenium complex [Re(L2)(CO)3Br] are shown to provide a method to position the nanoparticles at a water/dichloromethane interface forming a lustrous metal-like-liquid film (MeLLF) with a unique SERs response. The film formed using L2 showed divergent behavior in the presence of a range of metal ions whilst bound to the surface. [Re(L)(CO)3Br] (where L = 2,2´-bipyridine, L1 and L2) in solution demonstrates a selective interaction with Hg2+, observed by UV-vis, emission and 1H NMR spectroscopy, attributed to abstraction of the bromide. This interaction was demonstrated by subtle changes in the characteristic Raman Re-CO stretch at 510 cm 1 both with the MeLLF, and when the film is immobilized in a PVA surface-exposed-nano-sheet (SENS). The work provides proof of concept that the organometallic complexes can be employed as “labels” to generate SERS-active nanoparticle films that possess detection capabilities.

The Fletcher group has previously explored the ruthenium complexes of 4,4’-bis(benzoxazole-2-yl)-2,2’-bipyridine (BBOB), 4,4’-bis(benzothiazole-2-yl)-2,2’-bipyridine (BBTB), and 4,4’-bis(benzimidazole-2-yl-2,2’-bipyridine (BBIB) and shown that they typically bind in the minor groove of DNA, rather than intercalate, having a preference for defect sites such as bulges and hairpin loops. We report here the synthesis of a series of related ligands, and their complexation to both rhenium(I) and iridium(III), via reaction with Re(CO)5Br and {Ir(ppy)2(Cl)}2 respectively. These have been characterized through NMR, infrared and UV-Vis absorption and emission spectroscopy, illustrating the effect of conjugation of the extended heterocyclic structure. Despite solubility issues, we will discuss here the photophysical analysis, including circular dichroism (CD) spectroscopic studies, which show that these complexes interact with DNA and highlight a new potential DNA binding mode.

This research thesis concerns the synthesis of novel mononuclear ruthenium(II) polypyridyl complexes with one ligand functionalised with benzimidazole groups, and the investigation into their ability to interact with DNA and various anions using different techniques, such as UV/Vis absorbance and emission, 1H-NMR and circular dichroism spectroscopies. Various complexes of the form [Ru(bpy/phen)2(L)]2+ {where bpy = 2,2´-bipyridine, phen = 1,10-phenanthroline, L = 4,4-bis(benzimidazol-2-yl)-2,2-bipyridine (bbib), 4,4’-bis(amidobenzimidazol-2-yl)-2,2’-bipyridine (bbaib), 4,4ʹ-bis(benzimidazole-2-yl-methyl)-2,2ʹ-bipyridine (bbimb), 4,4ʹ-bis(benzimidazole-2-yl-carbonyl)-2,2ʹbipyridine (bbimbo)} were synthesised in their racemic forms. Absorbance, fluorescence and 1H-NMR titrations studies were used to investigate the interaction between the complexes and dihydrogen phosphate, acetate, chloride and bromide anions. The results indicated that [Ru(bpy)(bbib)]2+, [Ru(phen)(bbib)]2+ [Ru(bpy)(bbaib)]2+, [Ru(phen)(bbaib)]2+, [Ru(bpy)(bbimb)]2+ and [Ru(bpy)(bbimbo)]2+ have high levels of interaction with dihydrogen phosphate and acetate in aqueous environments and no interaction with bromide and chloride. Stability constants calculated for [Ru(bpy)(bbib)]2+, [Ru(phen)(bbib)]2+ [Ru(bpy)(bbaib)]2+ and [Ru(phen)(bbaib)]2+ suggest a 2:1 guest:host stoichiometry for dihydrogen phosphate and a 1:1 guest:host stoichiometry with acetate. UV/Vis absorption, luminescence and circular dichroism (CD) titration studies with calf thymus DNA (ct-DNA) were used to analyse the binding between the racemic complexes and ct-DNA. The results were insufficient to confirm whether interaction occurs between [Ru(bpy)(bbib)]2+, [Ru(phen)(bbib)]2+ [Ru(bpy)(bbaib)]2+, [Ru(phen)(bbaib)]2+, [Ru(bpy)(bbimb)]2+ and [Ru(bpy)(bbimbo)]2+ and ct-DNA. CD Thermal denaturation studies indicated a decrease in stability of ct-DNA structure in the presence of [Ru(bpy)(bbib)]2+, [Ru(phen)(bbib)]2+ [Ru(bpy)(bbaib)]2+ and

A modular approach has been designed for the synthesis of labelled nanoparticle films for targeted analyte detection using surface-enhanced Raman spectroscopy (SERS). Interfacial self-assembly of citrate-stabilised silver nanoparticles and photo-deposition of silver salts were employed as possible methods for the generation of reproducible SERS surfaces. The ability to label the platforms with the rhenium complex [Re(L1)(CO)3Br] where L1 is (2,2'-bipyridin-4-ylmethyl)-(1,2-dithiolan-3-yl)pentanoate were also made and assessed using SERS. The complex shows an ability to effectively label the structures via covalent interactions between the silver surface and the dithiol group of the ligand, evidenced by SERS. The complex can modify and position citrate stabilised nanoparticles at the interface between two immiscible liquids, demonstrating that the Re(I)-modified metal liquid-like films (MeLLFs) and surfaceexposed nanosheets (SENS) provide a simple and reproducible method for the synthesis of labelled SERS active surfaces. The [Re(L1)(CO)3Br] complex, also displayed a selective spectroscopic response to the presence of Hg2+ in solution which is believed to be Hg-facilitated Br removal and coordination of the solvent. This interaction was also observed using SERS after treating [Re(L1)(CO)3Br] functionalised MeLLFs and SENS with organic and aqueous solutions of Hg2+. This is evidenced by observable changes to the Re–CO vibration and the appearance of a peak attributed to some form of Hg–Br interaction. The Re(I) complex, [Re(L2)(CO)3(pyr)](PF6) containing a bis-(benzimidazole)-4,4′ -bipyridine, L2 showed individual photophysical responses to dihydrogen phosphate and acetate in solution. H2PO4- causes a sequential quenching while OAccauses a “switch off” of the emissive response. The [Re(L2)(CO)3(pyr)](PF6) and [Re(L2)(CO)3(L3)](BF4) complexes, where L3 is N-(4-pyridylmethyl)lipoamide also formed labelled MeLLF and SENS surfaces. Anion sensing was possible with the SENS