Abstract
The use of the gallium oxalate complex [Ga(ox)3]3− as a building block in the formation of a drug-drug salt with the antimicrobial agent proflavine (PF) as its proflavinium cation (HPF+), namely [HPF]3[Ga(ox)3]·4H2O, is reported together with the preparation of the potassium salt K3[Ga(ox)3] and the novel dimeric gallium(III) salt K4[Ga2(ox)4(μ-OH)2]·2H2O. All compounds have been characterized by solid state methods, and their performance as antimicrobial agents has been evaluated by disk diffusion assay against the bacteria strains Pseudomonas aeruginosa ATCC27853, Staphylococcus aureus ATCC25923, and Escherichia coli ATCC25922. While the [HPF]3[Ga(ox)3]·4H2O drug-drug salt is effective against all three strains, the gallium oxalate salt K3[Ga(ox)3] showed impressive selectivity towards P. aeruginosa, with little to no antimicrobial activity against the other two organisms. This work presents novel breakthroughs towards Ga based antimicrobial agents.
Highlights
The use of the gallium oxalate complex [Ga(ox)3]3− as a building block in the formation of a drugdrug salt with the antimicrobial agent proflavine (PF) as its proflavinium cation (HPF+), namely [HPF]3[Ga(ox)3]·4H2O, is reported together with the preparation of the potassium salt K3[Ga(ox)3] and the novel dimeric gallium(III) salt K4[Ga2(ox)4(μ-OH)2]·2H2O
The antimicrobial performance of these novel compounds against the bacteria strains Pseudomonas aeruginosa ATCC27853, Staphylococcus aureus ATCC25923, and Escherichia coli ATCC25922 using the established antimicrobial disk diffusion assay has been investigated and the results described in the following
The trianion [Ga(ox)3]3− in the salt K 3[Ga(ox)3]·3H2O is isostructural with octahedral oxalate complexes of di- and trivalent metals, such as zinc(II), chromium(III), iron(III), aluminum(III), among others
Summary
The use of the gallium oxalate complex [Ga(ox)3]3− as a building block in the formation of a drugdrug salt with the antimicrobial agent proflavine (PF) as its proflavinium cation (HPF+), namely [HPF]3[Ga(ox)3]·4H2O, is reported together with the preparation of the potassium salt K3[Ga(ox)3] and the novel dimeric gallium(III) salt K4[Ga2(ox)4(μ-OH)2]·2H2O. Co-crystallization methods based on the direct reaction in the solid state (or in slurry conditions) have proven to be well suited for the preparation of new compounds in the solid form for subsequent applications and uses in a variety of fields[3,4] One of these that is becoming increasingly important is that of microbe drug-resistance, i.e. the ability of bacteria to develop survival mechanism to evolve and protect themselves against the antimicrobial effect of pharmaceutical drugs, is increasingly affecting our ability to treat human and animal d iseases[5–7]. Our objective towards contributing to the quest for novel antimicrobials relies on an approach used successfully in previous occasions to prepare compounds possessing enzymatic inhibition capacity against enzymes such as amino-mono oxygenase and u rease[12,13] This approach utilizes crystal engineering methods, such as the direct reaction between preformed molecular salts, to combine organic biocides with metal atom complexes that possess antimicrobial properties. Proflavine antimicrobial mode of action is based on the Scientific Reports | (2022) 12:3673
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