## 6 Metal Complexes Based on Terpene Ligands and Their Biological Activities  
### The Reactivity of Terpenes  
To address the microbiological risk associated with adherent pathogenic bacteria and their biofilms in hospital and in food environments, many scientific disciplines have to be combined: organic chemistry to synthesize new molecules with antibacterial and antibiofilm effects; microbiology to assess their biological activity; and formulation to set up the best formula to enhance the antibacterial and antibiofilm activities and to deal with challenges related to these molecules such as solubility, volatility, and eco- and cytotoxicity. Coordination chemistry of transition metals and biologically active ligands is an active field of modern chemistry that incorporates contributions from asymmetric synthesis, metal complex catalysis, biochemistry, medicinal chemistry, and pharmacology [203; 204]. The current challenge is to set up highly reactive ligands for organic synthesis. Therefore, it is important to first study the coordination behavior of biologically active chiral ligands containing N and O donor atoms towards metal ions [205].  
The two chiral forms of a molecule, also known as enantiomers, have opposing spatial geometries and therefore interact with their environment differently. This feature is extremely important in medicinal chemistry [206; 207]. In the case of limonene, which is abundant in citrus fruit essential oils and has two enantiomers--one with a lemon smell ((S)-(-)limonene) and one with an orange smell ((R)-(+)-limonene)--the two enantiomers do not necessarily exhibit the same biological activity because they do not react with  
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Terpene Derivative** & **Structure** & **Bacteria** & **Reference** \\ \hline \multirow{8}{*}{**Menthol**} & \multicolumn{3}{c}{_Escherichia coli_} \\  & & _Pseudomonas aeruginosa_ & [194] \\  & & _Klebsiella pneumoniae_ & \\  & & _Staphylococcus aureus_ & \\ \cline{2-3}  & & _Escherichia coli_ & \\  & & _Staphylococcus aureus_ & \\  & & _Listeria tinocta_, & \\  & & _Saccharomycesces cercioca_ & \\ \hline \multirow{8}{*}{**Thymol**} & \multicolumn{3}{c}{_Enterobacter sakazakii_} & [196] \\ \cline{2-3}  & & _Salmonella Enteritidis_ & [10] \\ \cline{2-3}  & & _Aerononas hydrophilia_ & [197] \\ \cline{2-3}  & & _Methicillin-resistant Staphylococcus aureus_ & [198] \\ \cline{2-3}  & & _Escherichia coli_ & \\ \cline{2-3}  & & _Pseudomonas aeruginosa_ & [199] \\ \cline{2-3}  & & _Salmonella spp._ & \\ \cline{2-3}  & & _Pseudomonas aeruginosa_ & [200] \\ \cline{2-3}  & & _Enterococcus faecalis_ & \\ \hline \multirow{8}{*}{**Eugenol**} & \multicolumn{3}{c}{_Listeria monocytogenes CECT 933_} \\  & & _Escherichia coli ATCC 35218_ & \\ \cline{2-3}  & & _Pseudomonas aeruginosa PAO1_ & \\ \cline{2-3}  & & _Staphylococcus aureus ATCC 6538_ & \\ \cline{2-3}  & & _Escherichia coli ATCC 25922_ & \\ \cline{2-3}  & & _Escherichia coli_ & \\ \cline{2-3}  & & _Pseudomonas aeruginosa_ & ATCC 9027_ & \\ \cline{2-3}  & & _Pseudomonas aeruginosa_ & [202] \\ \cline{2-3}  & & _Staphylococcus aureus_ ATCC 25923_ & \\ \cline{2-3}  & & _Staphylococcus aureus_ & \\ \cline{2-3}  & & _Streptococcus mutans ATCC 0446_ & \\ \hline \hline \end{tabular}
\end{table}
Table 4: Cont.  
the same receptors [208,209]. An enantiomer of a medical molecule can have beneficial properties while the other is highly harmful. Nature is a high-level synthetic chemist, producing a wide range of chiral substrates with high stereochemical purity, particularly ligands based on natural molecule derivatives. Terpenes are among these molecules and can induce chirality and reactivity (Figure 3) due to the presence of double bonds in their structure, in addition to the ability to perform addition [210], rearrangement [211], cyclization, isomerization (Figure 4), and ozonolysis (O\({}_{3}\)) (Figure 5). Dehydration reactions can also occur in compounds derived from terpen with alcohol functions.