In order to exploit the untapped sensing potential of the TQEN (N,N,N′,N′-tetrakis(2-quinolylmethyl)ethylenediamine) family of fluorescent probes, 8-TQEN (N,N,N′,N′-tetrakis(8-quinolylmethyl)ethylenediamine) analogs were designed and characterized. Although 8-TQEN lacks practicality owing to poor solubility in both aqueous media and organic solvents, 6-MeO-8-TQEN (N,N,N′,N′-tetrakis(6-methoxy-8-quinolylmethyl)ethylenediamine, 1b) exhibits Cd²⁺-selective fluorescence enhancement at 395 nm in DMF–HEPES buffer (1 : 1), (I_Cd/I₀ = 25, λ_ex = 332 nm, ϕ_Cd = 0.025). Zn²⁺ induces weaker fluorescence (I_Zn/I₀ = 9, I_Zn/I_Cd = 0.35). In contrast, both the parent probes TQEN (I_Zn/I₀ = 23, I_Cd/I_Zn = 0.64) and 6-MeOTQEN (I_Zn/I₀ = 11, I_Cd/I_Zn = 1.29 exhibit higher sensitivity toward Zn²⁺. When the quinoline groups were replaced with 8-hydroxyquinoline different responses were observed. The propanediamine derivative, 8-TQOEPN (N,N,N′,N′-tetrakis(8-quinolyloxyethylene)propanediamine, 2c) exhibits significant fluorescence enhancement at 423 nm upon Cd²⁺ binding (λ_ex = 325 nm, I_Cd/I₀ = 19, ϕ_Cd = 0.31). Fluorescence enhancement is Cd²⁺-specific as Zn²⁺ induces only more modest emission increases (I_Zn/I₀ = 8.8, I_Zn/I_Cd = 0.45).