# In Silico SwissADME Analysis of Antibacterial NHC-Silver Acetates and Halides Complexes
## 1 Introduction  
\(N\)-Heterocyclic carbenes (NHCs) are organic compounds characterized by a carbene carbon atom located within a nitrogen-containing heterocyclic ring [1]. Although these compounds are reactive and difficult to isolate, the first successful isolation of a free NHC in 1991 paved the way for rapid advancements. Since then, NHCs have become widely used in organometallic chemistry, where they now rival traditional ligands like tertiary phosphines. NHCs are particularly well-known for their strong \(\sigma\)-donating properties, allowing them to form robust bonds with metals--often stronger than those formed by phosphines. This electron-rich nature influences various reactions, such as cross-coupling reactions, making NHCs highly versatile in catalytic applications. The bonding of NHCs with metals involves not just \(\sigma\)-donation but also \(\pi\)-backdonation, which is influenced by factors such as the saturation, aromaticity, and steric bulk of the NHC ligands. As a result, NHCs have been widely adopted in catalytic processes, including C-H activation and bond formation. Their ability to stabilize and activate metal centers has made them valuable in the development of novel materials and catalytic systems [2]. Silver is increasingly recognized for its ability to generate reactive oxygen species (ROS), which play a crucial role in their antimicrobial properties. The interaction of silver with biological systems leads to the production of ROS, including hydroxyl radicals and superoxide, which can induce oxidative stress in microbial cells, ultimately resulting in cell death [3; 4]. This oxidative stress is particularly pronounced in aerobic conditions, where bacteria exhibit heightened susceptibility to silver due to increased ROS generation [3; 5]. The mechanism by which silver induces ROS involves the release of silver ions (Ag\({}^{+}\)), which can interact with cellular components and disrupt metabolic processes, including the respiratory chain, leading to mitochondrial dysfunction and apoptosis [6; 7]. To enhance silver's proven antibiotic properties, \(N\)-heterocyclic carbenes (NHCs) can be incorporated as supplementary biomolecules. The transport of NHC-silver(I) complexes into bacterial cells is a crucial factor in boosting antibacterial activity. NHC-silver(I) complexes have attracted considerable interest in medicinal chemistry, especially for their potential as antibacterial [8; 9; 10; 11] and anticancer agents [8; 9; 10; 11; 12; 13; 14; 15; 16; 17]. The effectiveness of these complexes is closely linked to the structure of the NHC core and the nature of the substituents on the nitrogen atoms, which can be tailored to optimize properties like lipophilicity and the controlled release of silver ions within the intracellular environment. The antibacterial activity of NHC-silver complexes is primarily attributed to their ability to slowly release silver ions, which disrupt essential bacterial cell functions [18]. It is assumed that this antimicrobial activity is further enhanced by the lipophilicity of the complexes, which facilitates better penetration into bacterial cells and ensures a sustained release of active agents. Moreover, NHC-silver complexes have demonstrated efficacy against a broad spectrum of pathogens, including Gram-positive and Gram-negative bacteria, as well as fungi and yeast. This broad-spectrum activity underscores their potential as promising candidates for the development of new antimicrobial agents [11; 19]. The role of lipophilicity in enhancing the biological activity of NHC-silver complexes is especially critical, making it a focal point in the continued research and development of these compounds as potent antimicrobial and anticancer agents [20; 21; 22]. SwissADME is a web-based tool developed by the Swiss Institute of Bioinformatics (SIB) for predicting the drug-likeness, pharmacokinetics, and medicinal chemistry suitability of small molecules [23; 24].