## 1 Introduction  
Several metal ions play an important role in many biological processes, and, of course, in human physiology and their assumption through diet is important for our health, with the difference in amounts and qualities according to the age [1]. However, it is important the difference between nonessential and essential metals. Arsenic, cadmium, lead, and mercury are ubiquitous but do not play biochemical roles in humans. Furthermore, they are toxic and act in tissues by inducing several dangerous effects, mainly oxidative stress and interference with functions of essential cations such as magnesium and zinc [2]. Moreover, as studies confirm, lead is a risk for hypertension, while cadmium exposure promotes atherosclerosis through particular oxidative mechanisms, also because it can indirectly deplete antioxidants, such as glutathione, increasing reactive oxygen species (ROSs) [3]. On the contrary, some metal ions, such as copper, iron, and zinc, are essential for life, but their excess can also cause diseases. As an example, several researchers suggest a correlation between metal dyshomeostasis and neurodegenerative disorders [4]. In particular, many studies suggest that metals are involved in \(\beta\)-amyloid precipitation, causing neuronal damage in Alzheimer's disease (AD) [5], and one of the hypotheses related to Parkinson's disease (PD) is linked with high Fe levels in the brain that probably contribute to the deposition of Lewy bodies containing \(\alpha\)-synuclein [5]. Amyotrophic lateral sclerosis (ALS) and prion protein disease (PPD) seem to be pathologies in which the biometals can play a crucial role as well [6]. A potential way to treat metal poisoning and to reduce symptoms of diseases involving metal dyshomeostasis is chelation therapy. The term \"chelation\" is derived from the Greek word \"chela\",meaning the claw of the lobster and other crustaceans): it is suggested for caliper-like groups that function together as two units connecting a central metallic atom, forming heterocyclic rings [7]. Chelators bind metal ions and enhance their excretion, in order to cause a progressive decrease in their body concentration. Therefore, chelation therapy requires compounds with specific pharmacodynamic and pharmacokinetic characteristics which depend on the physical and chemical properties of the metal and the chelating group itself such as ionic radius, solvation sphere size and deformability, hardness/softness of electron donors and acceptors, bioavailability, metabolism, organ, and intra/extracellular-specific compartmentalization [8]. Moreover, the thermodynamic, kinetic, and redox stability of the compounds is considered important. Although several chelators exhibit high thermodynamic stability and inertness, their redox potential falls itself into the range of ROS production [9]. An excellent chelator should have selectivity towards a specific target metal ion and should have low toxicity both as a free chelating agent and as a formed complex [10]. Another important requirement of chelating agents used for the treatment of neurodegenerative diseases is the ability to cross the blood-brain barrier (BBB). Consequently, a significant number of metal chelators are excluded because of their hydrophilicity [6]. Chelators can be classified on the basis of donor atoms involved, ring size (four-, five-, or six-membered), charge of the complex, or number of bonds between metal and chelating molecules (monodentate 1:1, bidentate 1:2, tridentate 1:3, tetradentate 1:4) [11]. The choice of a suitable chelating group for each metal ion is based on [PERSON]'s theory of Hard and Soft Acid and Bases (HSAB; Table 1), that classifies Lewis acids and bases as hard, soft and borderline. \"Hard\" acids (named class (a) by [PERSON]) prefer to bind \"hard\" or nonpolarizable bases; on the contrary, \"soft\" acids, or class (b), bind preferentially \"soft\" or polarizable bases [12].