Novel Antibacterial Azelaic Acid BioMOFs

Abstract

The development of metal–organic frameworks (MOFs) for bioapplications has gained great relevance over the last few years, mainly due to their potential as drug carriers and/or imaging agents. Although the bioactive azelaic acid has also been widely used as an antibacterial and anti-inflammatory drug, it presents low solubility, so of utmost importance is the development of more soluble formulations with sustained activity. In this contribution, we prove that new azelaic acid-based metal biomolecule frameworks (BioMOFs) are a viable pathway to achieve this goal. Therefore, five novel MOFs were prepared by a simple, low-cost, and environmentally friendly mechanochemical approach, combining azelaic acid with endogenous cations (i.e., K+, Na+, and Mg2+): [K2(H2AZE)­(AZE)] (1), [Na4(HAZE)4] (2), [Na2(AZE)­(H2O)] (3), and two different polymorphic forms of [Mg­(AZE)­(H2O)3] (4) and (5) (where H2AZE - neutral azelaic acid; HAZE - mono-deprotonated azelaic acid; AZE - di-deprotonated azelaic acid). After full structural characterization using single-crystal X-ray diffraction data and other complementary standard solid-state techniques, their thermal and moisture stabilities as well as aqueous solubility were assessed. Finally, their antibacterial activity was evaluated against two Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis), commonly present on the skin. All MOF materials exhibit good stability and higher solubility than azelaic acid. In addition, BioMOF 1 has shown good antibacterial activity both at pH 5 and 6.5. Thus, 1 has shown to be a promising candidate to further develop new topical formulations of H2AZE.

The Lisbon Supramolecular Green Story: Mechanochemistry towards New Forms of Pharmaceuticals

“…gabapentin lactam [28], the anti-hipertensive perindopril erbumine [29], and bismuth salicylate [30] that we are not referring to here, as they were done in straight collaboration with other international labs or the Portuguese industry. In all these works we used mechanochemistry as a synthetic technique, which we are also applying in the group in another context, which is that of API coordination networks [31].…”

Mechanochemistry in Portugal—A Step towards Sustainable Chemical Synthesis

“…Azelaic acid is used to treat mild to moderate acne, and it is usually available as topical formulations, often affected by its low aqueous solubility. Quaresma et al designed, synthesized, and characterized five new azelaic acid MOFs with Mg(II), K(I), and Na(I) [ 83 ]. It is worth noting that depending on the mechanochemical reaction conditions, different polymorphic forms were obtained with Mg(II) and with Na(I), with two different forms of each being reported.…”

Silver(I)-Tazobactam Frameworks with Improved Antimicrobial Activity

“…MOFs based on bioactive components (BioMOFs) are an emerging subclass of MOFs, constructed from a variety of metals and ligands such as amino acids, peptides, nucleobases, saccharides, active pharmaceutical ingredients, and enzyme inhibitors ( Rojas et al, 2017 ; An et al, 2019 ; Cai et al, 2019 ; Quaresma et al, 2020 ). Due to the low steric hindrance, low toxicity, and good biocompatibility of bioligands, BioMOFs are currently widely studied for possible applications in several areas including biomedicine ( Sun et al, 2020 ) and biocatalysis ( Celik et al, 2018 ).…”