# Metal-Coordinated Polymer-Inorganic Hybrids: Synthesis, Properties, and Application
## 3 Polymer-Inorganic Coordinated Hybrids: Complexation-Induced Properties
### Therapeutics, Sensing, and Polyelectrolytes  
Polyethyleneimine (PEI) is a common choice for forming complexes with metals due to its abundant free amino groups, which can coordinate with metal ions through electrostatic interactions or coordination bonds. PEI contains primary, secondary, and tertiary amines, with approximately 25% of the nitrogen atoms being primary, 50% secondary, and 25% tertiary. The study emphasizes that the binding of metal ions is mainly facilitated by these amine groups, with primary amines playing a particularly crucial role. When PEI is chemically modified by acetylation or alkylation, which blocks the primary amines, there is a significant decrease in the polymer's ability to bind metal ions. The mechanism of metal ion complexation described by [PERSON] and coworkers [115] involves a cooperative binding process. The binding of metal ions, especially Cu\({}^{2+}\), induces a conformational change in the PEI structure, causing the polymer chains to swell or unfold. This unfolding increases the exposure of additional amine groups that were previously buried within the polymer matrix, allowing more metal ions to bind. This behavior is evident in the cooperative nature of the binding isotherms, where there is a steep increase in metal ion uptake as the free metal ion concentration rises, particularly pronounced for Cu\({}^{2+}\). PEI is commonly employed in a range of applications, including biomedical, molecular imaging [116], drug delivery [117; 118], and wastewater treatment. Its strong metal-binding properties make it suitable for designing metal-based complexes, particularly for DNA binding in anticancer therapies. PEI is regarded as one of the most efficient polymers for transfection, both in vitro and in vivo. Its high density of amine groups contributes to its DNA-condensing ability and its interaction with cell membranes, facilitating uptake. However, a significant drawback of PEI is its high cationic charge density, which is associated with cytotoxicity. While lower-molecular-weight PEI is less toxic, it also demonstrates reduced transfection efficiency. This tradeoff has driven research efforts to modify PEI, such as incorporating biodegradable linkages, to improve its biocompatibility without sacrificing its effectiveness. These modifications aim to create safer PEI-based systems for clinical applications [119]. [PERSON] et al. [120] synthesized water-soluble PEI-copper(II) complexes using phenanthroline and L-tyrosine as co-ligands (Figure 7a). Their study showed that the DNA-binding affinity of these complexes increased with the number of copper centers in the polymer. Thermal denaturation studies indicated that higher coordination degrees contribute to improved DNA stability, as the complexes stabilize the DNA double helix. The paper also describes significant cytotoxic activity of the most highly coordinated polymer-copper(II) complex against MCF-7 breast cancer cells, with apoptosis being the primary mode of cell death, confirmed through various assays that detect DNA fragmentation and apoptotic morphology. Figure 7b further supports these findings by showing AO/EB-stained photomicrographs of MCF-7 cells treated with the complexes, highlighting apoptotic changes such as chromatin condensation and membrane blebbing, alongside quantitative data indicating an increase in apoptotic cells over time. PEI-Au hybrids have been developed for simple and sensitive colorimetric sensors for detecting copper ions (Cu\({}^{2+}\)) (Figure 7c) [121]. The team synthesized the PEI/Au NPs by employing polyethyleneimine (PEI) as a reducing and stabilizing agent without the need for additional nanoparticle seeds or stabilizers. The detection mechanism hinges on the specific interaction between Cu\({}^{2+}\) ions and the amino groups present on the PEI, which results in a color change from wine red to purple, providing a visual indication of a copper ion presence.