Development of Highly Selective Fluorescent “Turn‐On” Schiff Base Probes for Serum Albumins

ABSTRACT Serum albumin, the major plasma protein is a key health indicator for disease diagnosis and its precise detection in body fluid through various analytical techniques has gained significant research interest. This study introduces two maleonitrile tethered amine‐imine functionalized tetradentate Schiff bases, 2‐((E)‐2‐hydroxybenzylideneamino)‐3‐(pyridin‐2‐ylmethylamino)maleonitrile (1) and 2‐((E‐4‐(diethylamino)‐2‐hydroxybenzylidene)amino)‐3‐((pyridin‐2‐ylmethyl)amino)maleonitrile (2) , which act as a fluorescent “Turn‐On” probe upon interaction with human serum albumin (HSA) and bovine serum albumin (BSA). The synthesized sensors can detect serum albumins with excellent selectivity in the presence of various bio‐analytes. The remarkable increase of fluorescence intensity of the two weakly emissive sensors upon addition to serum albumins revealed significant binding between them with high sensitivity. Sensor 2 with an additional diethyl amine group has higher sensitivity and binding constants than sensor 1 . Site‐selective competitive replacement by standard markers along with molecular docking studies suggested the probable binding sites of the two sensors were at site 3 of the sub‐domains IB of serum albumins. The sensors can quantitatively estimate HSA in urine samples, validating their practical use. The low limit of detection and highly efficient detection of serum albumin by these easy and cost‐efficient sensors could be a good replacement for known sensing methods of serum albumin.