# Antimicrobials in Dentistry
## 2 Antimicrobials Used in Dentistry
### Antibacterial Monomers in Dental Restorative Systems
#### 2.4.1 Eugenol and Eugenyl Methacrylate  
Eugenol (4-allyl-2-methoxyphenylenol), a member of the allybenzene class of chemical compounds, is a major constituent (72-90%) of the essential oil extracted from cloves. Cloves are the flower buds found on the tree in the family _Myrtaceae_, _Syzgium aromaticum_. Figure 2: Chemical structure of (meth)acrylate (R\({}_{1}\)) monomers bearing antibacterial pendant groups (R\({}_{2}\)). Eugenol possesses analgesic, anti-inflammatory, antifungal and antibacterial activity. It has been used in dentistry since the 19 th century due to its ability to relieve pain in irritated or diseased tooth pulp. Currently, it is available as a pulp capping agent, root canal sealer and temporary filling material in combination with zinc oxide in the form of zinc oxide eugenol (ZOE). Eugenol inhibits the growth of several microorganisms, including facultative anaerobes commonly isolated from infected root canals, and produces a soothing effect on the pulp [78]. However, unreacted eugenol in ZOE cements may produce tissue irritation and induce an inflammatory reaction in the oral mucous membranes. Another drawback of ZOE cements is their weak mechanical properties, as demonstrated by their low strength, poor resistance to abrasion, and disintegration in the oral cavity with time [79; 80]. Moreover, ZOE cements interfere with the polymerisation reaction of methacrylate-based restorative resins due to the remaining free eugenol [81; 82]. Eugenol is a strong antioxidant and a potent free-radical inhibitor, which can cause a detrimental effect on the physical and mechanical properties if an overlying permanent dental resin-based composite material is used. Thus, complete cleaning of the tooth cavity of any residual eugenol is necessary if a restoration that cures via free-radical polymerisation is to be applied. However, modifying the chemical structure of eugenol by incorporating a polymerisable group, i.e., a methacrylate group, allows the eugenol derivative to participate in polymerisation reactions rather than inhibit them [83; 84]. Hence, the incorporation of this new derivative can be advantageous in the field of dental materials or bone cements [84], whilst benefitting from the bactericidal effects of eugenol. An acrylic derivative of eugenol was synthesised through Fischer esterification [83] using stoichiometric amounts of eugenol and triethylamine dissolved in diethyl ether and reacted with an excess of methacrylol chloride at room temperature under nitrogen atmosphere (Figure 3). The triethylamine chlorhydrate formed was removed from the reaction medium and unreacted reagents eliminated through successive extraction and purified via flash distillation and column chromatography to yield eugenyl methacrylate. The acrylic derivative of eugenol, in which the acrylic residue is directly bonded to the aromatic ring of eugenol, was successfully synthesised directly from eugenol with a product yield of 80%. The esterification reaction was confirmed by NMR and FTIR spectroscopies showing presence of the bands corresponding to the methacrylic residue [83]. The antibacterial activity of EgMA was initially tested against _Streptococcus mutans_ and _Escherichia coli_, the most common species found in medical and dental surgical sites and devices. The data suggest that the conjugated double bond in the aromatic structure of EgMA and the allylic side chain are responsible for the strong inhibitory effects of  
Figure 3: Synthetic scheme of the Fisher esterification of the eugenol molecule yielding its derivative eugenyl methacrylate [80]. this compound [84]. In addition, the alkyl substitution into the phenol nucleus alters the distribution ratio between the aqueous and the non-aqueous bacterial phases by reducing the surface tension (hydrophobicity of the compounds) or altering the species selectivity [85]. Thus, modification of the chemical structure of the eugenol molecule yielding an \(\alpha\)-unsaturated ester, EgMA, resulted in a good hydrophobic balance with a certain proton exchange capacity.