Revisiting the antimicrobial potential of metalloporphyrins: from food to pharma

Abstract

Porphyrins, their derivatives, and metal ion complexes – particularly copper-substituted forms such as Cu-Chl, Cu-Chln, and Na-Cu-Chln – are increasingly recognized for their broad-spectrum antimicrobial properties. However, in the context of terminological and trivial confusions in food chemistry and pharmaceuticals, data on the chemical properties and biological activity of porphyrins remains fragmented and lacks comprehensive systematization. This review adopts a cross-disciplinary mapping approach to clarify the chemical structures, nomenclature, antimicrobial properties, and the presented mechanistic insights of porphyrins and their derivatives, highlighting their significance in both the food and pharmaceutical industries. As a result of the mapping systematization, porphyrins have been remarked as current and potential antimicrobial agents, with a specific emphasis on the compounds such as Cu-Chl, Cu-Chln, and Na-Cu-Chln. Copper complexation has been shown to enhance biological activity while maintaining low toxicity profiles. Emphasis is placed on Cu-Chl, Cu-Chln, and Na-Cu-Chln, which demonstrate promising properties and applications in nutraceuticals and therapeutics. Their bactericidal properties, which resulted in combating antibiotic-resistant infection-causative pathogens, are particularly interesting, especially in the era of addressing global challenges such as antibiotic resistance. This conceptual review remarks on the critical gaps in current knowledge and accentuates the need for systematic studies to optimize the clinical and industrial applications of porphyrins.

Introduction

The use of porphyrins in medical practice was historically preceded by the observation of photodynamic effects at the beginning of the twentieth century and led in the 1970s through 1990s to the clinical use of photodynamic therapy with hematoporphyrin derivatives and Photofrin (Ochsner Citation1996; Wagnières et al. Citation1997). In parallel, the semi-synthetic analog, chlorophyllin, was explored in the 1940s–1950s as a wound dressing, odor suppressant in ostomy patients, and has been used in regulated amounts in food and medicine, since the late 1980s as the food colorant E141, and currently in the twenty first century, Cu-Chln continues to find its applications (Lam and Brush Citation1950; Dashwood Citation1997; Dashwood et al. Citation2013).

Porphyrins, characterized by their tetrapyrrole macrocyclic ring, are essential in both biological and industrial processes. From the chemical point of view, all porphyrins are characterized by the same core structure – four pyrrole units otherwise known as porphin (porphyrin nucleus) (Richardson et al. Citation2005). Structural modifications – such as variations in conjugation or the number of heteroatoms – can generate a range of tetrapyrrole compounds, including naturally occurring derivatives like chlorins (van Eldik 2016). Additionally, the porphyrin ring has four meso-positions, which are highly reactive and can undergo various chemical reactions (Sobotta et al. Citation2019; Vesselli Citation2020). Due to the presence of the highly stable conjugated macrocyclic ring structure, porphyrins easily chelate via four methine bridges with a number of metal ions such as Fe, Zn, Cu, Mg, Co, and Ni, known as metalloporphyrins (Sobotta et al. Citation2019; Vesselli Citation2020).

Metalloporphyrins linked with Mg, Fe and Co are widely distributed in living tissues where they participate in vital biochemical processes, such as oxygen transport (e.g. haemoglobin) and photosynthesis (e.g. chlorophyll) (Figure 1) (Amos-Tautua et al. Citation2019). Also, metalloporphyrins are involved in the transport of electrons through cytochromes b and c, as well as in the oxidative reactions in the processes of cytochrome P450, cytochrome oxidase, and cobalamin (vitamin B12) (Amos-Tautua et al. Citation2019).

Figure 1. Tetrapyrrole ring (porphin) and its derivatives (Kloehn et al. 2021).

Chlorophylls (Chls), present in plants, cyanobacteria, and algae is one of the most widely distributed metalloporphyrins and is a Mg complex found in all photosynthetic microorganisms (Gruznov et al. Citation2024). While Chls refer to natural compounds, chlorophyllins (Chlns) represent semi-synthetic Chl derivatives. The production of Chlns involves the hydrolysis (saponification) of natural Chls which increases water solubility. Then, the Mg2+ ion is substituted to other metal ions (e.g. Cu2+). Noteworthy, if copper replaces the central magnesium atom in the chlorophyll molecule, the semi-synthetic pigment known as Cu-Chln is obtained (Zhong et al. Citation2021; Ebrahimi et al. Citation2023). This modification enhances water solubility and bioavailability, making Chlns suitable for oral administration applications such as dietary supplements and food colorants (Ferruzzi and Blakeslee Citation2007; Gomes et al. Citation2009; Martins et al. Citation2023). Additionally, cationic porphyrins have been especially effective as photodynamic agents against microbes, showing good antibacterial and antifungal activities (Sobotta et al. Citation2019).

Given the current global issues of antibiotic resistance and the decline in antibiotic discovery, the search for other forms of antimicrobial agents has become very important, and with this, Cu-associated porphyrins mentioned in recent studies highlight their broad-spectrum antimicrobial potential, particularly in photodynamic contexts (Sobotta et al. Citation2019).

Therefore, this mapping review focuses on summarizing the biological activities, chemical relevancy, and therapeutic application of porphyrins, porphyrin derivatives, and their metal ion complexes. The aim of systematic mapping review (Sutton et al. Citation2019) is to provide a broad evaluation of the current state of knowledge, categorizing the existing literature regarding investigated compounds and their diverse bioactive applications. In addition, the review aims to highlight the mechanisms that are responsible for the antimicrobial properties of the compounds based on the current research findings and also seeks to describe how these compounds can be used and are utilized in food industry. In light of the above, throughout the structured approach, this work not only consolidates fragmented data, but also aims to establish possible research gaps in the current knowledge and potential recommendations that can help to advance the frontiers of these versatile bioactive compounds in clinical and industrial use.

The methodology for the search and selection of research articles was conducted systematically, utilizing academic databases, including Web of Science and Google Scholar. The aim was to collect a broad range of studies focusing on copper-substituted porphyrins, particularly regarding their biological activity and potential applications. The keywords (i.e. Copper-substituted porphyrins; Copper porphyrins biologic activity; Copper porphyrin antimicrobial; Copper porphyrins bacteria biofilm; Cu porphyrins cytotoxicity; Cu porphyrins application; Naturally occurring chlorophylls/porphyrins; Cu-substituted chlorophylls (Cu-porphyrins); Antibacterial activities of porphyrins) used for the literature review were specifically chosen to capture the wide scope of relevant research related to copper porphyrins and their biological interactions.

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Revisiting the antimicrobial potential of metalloporphyrins: from food to pharma, Igori Balta, Marta Žogota, Nicolae Corcionivoschi, Irina Chiorescu, Oleksandr Dobrovolnyi, Stefan Batrina, Ioan Pet, Aurelia Coroian, Andrejs Sitovs, Lavinia Ștef & Valentyn Mohylyuk, Received 03 Feb 2025, Accepted 29 Oct 2025, Published online: 07 Nov 2025, https://doi.org/10.1080/1040841X.2025.2584078