Copper coordination complexes targeting fungal biofilms: a systematic review

Copper coordination complexes have attracted increasing attention as tunable systems for antifungal applications, particularly in biofilm-associated infections. This systematic review evaluates their antibiofilm activity against opportunistic fungal pathogens, with emphasis on coordination-driven structure-activity relationships. The objective was to assess how ligand donor set, nuclearity, coordination number, and geometry influence antifungal behavior. Original studies (2015–2025) investigating molecular copper complexes and reporting biofilm-related outcomes against Candida, Cryptococcus, or Aspergillus were included, while nanoparticles and systems lacking well-defined coordination environments were excluded. Searches were conducted in PubMed/MEDLINE, Web of Science, and Scopus (last search: February 5, 2026). Risk of bias was assessed using predefined criteria, and results were synthesized qualitatively due to heterogeneity. Six studies were included, comprising seven copper(II) complexes, predominantly mononuclear N- or mixed N,O-donor species, with coordination numbers from four to six. These compounds showed inhibition of biofilm formation (≈10–70%) and limited activity against established biofilms (MBEC = 31.25–61.6 µg/mL). Mechanistic evidence was limited and heterogeneous. The small number of studies and variability in experimental methods limit robust structure–activity correlations. Nevertheless, copper coordination complexes represent a promising platform for antifungal antibiofilm design. Protocol registered at the Open Science Framework (https://osf.io/k4r8j).