Bis(2-quinolylmethyl)ethylenediaminediacetic acids (BQENDAs), TQEN–EDTA hybrid molecules as fluorescent zinc sensors

Abstract

Molecular hybrids of TQEN (N,N,N′,N′-tetrakis(2-quinolylmethyl)ethylenediamine) and EDTA (ethylenediamine-N,N,N′,N′-tetraacetic acid) were examined as fluorescent Zn²⁺ sensors. Upon the addition of Zn²⁺, N,N-BQENDA (N,N-bis(2-quinolylmethyl)ethylenediamine-N′,N′-diacetic acid, 1a) exhibits a 30-fold emission enhancement at 456 nm (λ_ex = 315 nm, ϕ_Zn = 0.018) in buffer (HEPES, pH = 7.5, 100 mM KCl). The fluorescence enhancement is Zn²⁺-specific as Cd²⁺ induces much smaller increases (I_Cd/I₀ = 5 and I_Cd/I_Zn = 16%). These spectroscopic properties, as well as the excellent water-solubility, represent a significant improvement compared to the parent TQEN sensor (ϕ_Zn = 0.007, I_Cd/I_Zn = 64%). The isoquinoline analog N,N-1-isoBQENDA (N,N-bis(1-isoquinolylmethyl)ethylenediamine-N′,N′-diacetic acid, 1b) possesses a similar Zn²⁺ fluorescence response to the parent 1-isoTQEN (N,N,N′,N′-tetrakis(1-isoquinolylmethyl)ethylenediamine) sensor, but exhibits diminished fluorescence intensity. Apo 1a and 1b extract more than 50% of the Zn²⁺ from an equimolar amount of [Zn(TPEN)]²⁺ (TPEN = N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine) or [Zn(EDTA)]²⁻, whereas TPEN and EDTA cannot effectively remove Zn²⁺ from [Zn(1a)] and [Zn(1b)]. The reduction of steric crowding in [Zn(TQEN)]²⁺ resulting from the substitution of two quinolines with carboxylates enhances the interaction between the metal ion and the remaining quinoline nitrogen atoms. The stronger bonding interaction results in enhanced emission intensity, Zn²⁺ selectivity and metal ion affinity. This is in contrast to [Zn(1-isoTQEN)]²⁺ where the isoquinoline-carboxylate replacement does not relieve any coordination distortion, therefore no significant changes in fluorescence or metal binding properties are observed.