Exploring the Co-Crystallization of Kojic Acid with Silver(I), Copper(II), Zinc(II), and Gallium(III) for Potential Antibacterial Applications

Abstract

Co-crystallization of kojic acid (HKA) with silver(I), copper(II), zinc(II), or gallium(III) salts yielded three 1D coordination polymers and one 0D complex in which kojic acid was present as a neutral or anionic terminal or bridging ligand. All reactions were conducted mechanochemically via ball milling and manual grinding, or via slurry. All solids were fully characterized via single-crystal and/or powder X-ray diffraction. As kojic acid is a mild antimicrobial compound that is widely used in cosmetics, and the metal cations possess antibacterial properties, their combinations were tested for potential antibacterial applications. The minimal inhibition concentrations (MICs) and minimal biocidal concentrations (MBCs) for all compounds were measured against standard strains of the bacteria P. aeruginosa, S. aureus, and E. coli. All compounds exerted appreciable antimicrobial activity in the order of silver, zinc, copper, and gallium complexes.

Keywords: antimicrobial metals; antimicrobials; co-crystallization; copper; gallium; mechanochemistry; silver; zinc.

Scheme 1

Kojic acid (HKA) and its monodeprotonated kojiate anion (KA⁻).

Scheme 2

The products of the reactions of kojic acid with (a) silver(I), (b) copper(II), (c) zinc(II), and (d) gallium(III) salts.

Scheme 3

Details of the slurry, ball milling, and crystallization processes for the preparation of [Ag(HKA)(NO₃)]∙H₂O.

Figure 1

Coordination around the silver(I) ion in crystalline [Ag(HKA)(NO₃)]∙H₂O (a). The 1D ribbon, extending along the crystallographic a-axis, formed by the silver–oxygen backbone and the coordinated kojic acid molecules and nitrate ions (b,c) (H_CH atoms not shown for clarity). View of the packing down of the crystallographic b-axis, showing the water molecules (in blue) filling in the channel in between the 1D ribbons (d) (H atoms not shown for clarity). Water oxygen in blue, nitrate oxygens in cyan, and silver ions in light grey.

Scheme 4

Details of the slurry, ball milling and crystallization processes for the preparation of Cu(KA)₂.

Figure 2

Square-pyramid polyhedra of oxygen atoms around the copper(II) cation in Cu(KA)₂ (a); the 1D zig-zag chains are shown here (b); side-by-side, linked via O⁻⋯(H)O_CHOH hydrogen bonds (c). Copper ions are in dark orange.

Scheme 5

Details of the slurry, ball milling, and crystallization processes for the preparation of Zn(KA)₂.

Figure 3

The 1D coordination polymer (a) extending along the (010) direction in crystalline Zn(KA)₂; note how the six-membered rings are π-stacked within the chain at a distance of ca. 3.2 Å. 1D chains are arranged parallel to each other in the crystal (b). Zinc(II) cations are blue-grey.

Scheme 6

Details of the slurry, ball milling and crystallization processes for the preparation of [Ga(KA)₂(OH₂)₂][NO₃]∙H₂O.

Figure 4

Crystalline [Ga(KA)₂(OH₂)₂][NO₃]∙H₂O: (a) Octahedral coordination around the Ga³⁺ cation, and (b) intercalation of nitrate anions/water molecules between wavy layers of cations extending along the b-axis direction. (H atoms not shown for clarity). Water oxygens are in blue (coordination sphere) and light blue (external); nitrate oxygens are in cyan, and nitrogens are in violet.

Figure 5

Kirby–Bauer disk-diffusion assay on LB agar plates. Distance zones were normalized to that of AgNO₃ as a value of 1.0. The taller the bar, the more antimicrobial the compound is. Standard errors are presented from 3–5 trials.