Heterocyclic Crown Ethers with Potential Biological and Pharmacological Properties: From Synthesis to Applications  
[PERSON]  
1 Department of Chemistry, Quaid I Azam University, Islamabad 45320, Pakistan; [EMAIL_ADDRESS]  
[PERSON]  
2 Institute of Chemistry, University of Sargodha, Sargodha 40100, Pakistan; [EMAIL_ADDRESS] (T.A.K. ); [EMAIL_ADDRESS] (J.I. ); [EMAIL_ADDRESS] (M.F.u.R.) 2 Department of Chemistry, International Islamic University, Islamabad 45320, Pakistan; [PERSON]]  
2 Department of Chemistry, Allama Iqbal Open University, Islamabad 45320, Pakistan; [EMAIL_ADDRESS]  
2 Department of Chemistry, Sub Campus, University of Sargodha, Bhakkar 30000, Pakistan; [EMAIL_ADDRESS]  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
2  
These can be either substituted or unsubstituted and possess a hydrophobic ring surrounding a hydrophilic cavity, enabling them to form stable complexes with metal ions and contributing to host-guest chemistry [1; 5]. Since their discovery, they have an outstanding capability to selectively coordinate ions, making them attractive for broad research applications [6]. The binding ability of crown ethers either with organic molecules or ions depends on their cavity size. They can carry different ions in a non-aqueous solvent. Crown ether also acting as a phase transfer catalyst. For example, 18-crown-6 shows binding ability with K\({}^{+}\) ion, and 12-crown-4 tends to complex with Li\({}^{+}\). Owing to this unique ability, CEs have broad applications in chemistry, biotechnology, and biochemistry. Alkali metal complexes with macrocyclic ligands mediate electron transfer processes. \[2\text{M(S)}+\text{L}{\rightarrow}\text{M}^{+}\text{L}+\text{M}^{-} \tag{1}\]  
where M is the alkali metal, e.g., potassium or sodium, and L is the complexant, e.g., 18-crown-6 as shown in Scheme 1 [7]. The complex compounds, in which metal cation acts as guest and crown ether acts as the host, fall into the class of host-guest chemistry. Complex properties and manufacturing of crown ether were first studied by [PERSON] in 1967 [9; 10]. According to [PERSON]'s proposal, it is the electrostatic force of attraction between the metal cation and the oxygen atoms of the crown ether ring (host-guest complexes). Crown ethers behave as ligands in host-guest complexes and have a much weaker attraction for transition-metal cations than for alkali and alkaline earth metal cations [5]. This class acts as chiral selectors for the enantiomeric separation of different chiral compounds. Polyether (18-crown-6) has a strong binding ability with protonated chiral primary amines [11]. CEs change their color when they bind with an ion like sodium. There's an option that it can be engaged to make ion detectors. Nanoparticle improved with crown ethers can be used as metal ion sensors charged molecules in colorimetric methods [12]. In the name of CEs, the first number refers to the number of atoms in the ring, and the second number represents atoms of oxygen. The oxygen atom behaves as a Lewis base. Hexaether is the first CE that was accidentally found during the synthesis of bisphenol [5]. Crown ether and its derivatives have also been reported to show various biological properties [1]. Crown ether and cryptand complexes of alkali metals show tremendously low ionization potentials (1.52 eV) and act as super-alkalis. This innovation opens a novel track in designing chemical species with record low ionization potentials and synthesizing multiple charged Zintl clusters [13]. The first compound was discovered as dibenzo-18-crown-6 (0.4%) during the synthesis of the phenolic ligand from catechol and bis(2-chloroethyl)ether. It was 18-carbon atoms cyclic ring with 6-oxygen atoms and complexed with sodium cation [14].