Colorimetric Glucose Detection Using Copper Complexes and Filter Paper-Based Simulated Skin Analysis: Influence of Methyl Substituted Phenolato Groups

Copper complexes [Cu2LA(OAc)2]
(1) and [Cu2LB(OAc)2] (2) were synthesized using Schiff base ligands H2LA and H2LB (where H2LA= 2,2’-((1E,1’E)-((piperazine-1,4-diylbis(ethane-2,1-diyl))bis(azaneylylidene))bis(methaneylylidene))diphenol),
and H2LB = 2,2’-((1E,1’E)-((piperazine-1,4-diylbis(ethane-2,1diyl))bis(azaneylylidene))bis(methaneylylidene))bis(4
methylphenol). Complexes 1 and 2 act as
copper-based colorimetric sensors for glucose through a cascade reaction
mechanism: GOx converts glucose to gluconic acid and generates H2O2, which acts as a substrate for the copper compound
oxidizing o-phenylenediamine (OPD) to form oxidized
OPD (oxOPD) detectable at 424 nm. The effects of incubation time and
pH on the catalytic activity of compound 2 were systematically
evaluated. Under optimized reaction conditions, the Michaelis constants
(Km) for compounds 1 and 2 were determined to be 0.00267 and 0.00251 M, respectively,
values comparable to those reported for various peroxidase systems
and previously reported enzyme mimics. Further mechanistic studies
indicated that the catalytic activity of these compounds is primarily
due to the generation of hydroxyl radicals (·OH).
Porous microneedles fabricated with simulated skin were utilized for
glucose monitoring. The integration of the copper compounds with glucose
oxidase (GOx) produced a distinct colorimetric response, changing
from white to yellow in the presence of varying glucose concentrations.
This approach highlights the potential for noninvasive and visually
detectable glucose sensing. The ground-state geometries of complexes 1 and 2 were optimized using B3LYP-level density
functional theory (DFT) calculations, and additional calculations
confirmed the structural stability and involvement of the LCu(II)-OOH
like species.