A Bis(Acridino)-Crown Ether for Recognizing Oligoamines in Spermine Biosynthesis

Abstract

Biogenic aliphatic oligoamines such as putrescine, cadaverine,
spermidine, and spermine are naturally occurring compounds
synthesized by enzymatic decarboxylation of amino acids. These
molecules play vital roles in biological systems, including cell
proliferation, gene expression, and nucleic acid stabilization.
Abnormal levels of these oligoamines are associated with various
diseases; for example, elevated spermine levels can be linked to
the presence of cancer cells, while decreased levels are observed
in aging-related illnesses like Parkinson’s disease.
A new bis(acridino)-crown ether was designed to selectively detect protonated oligoamines based on their chain length. The receptor contains two 18-crown-6-type macrocycles and two acridine units that provide strong fluorescence signaling upon guest
binding. The design enables it to distinguish between short- and
long-chain oligoamines through fluorescence intensity shifts.Two
synthetic strategies were developed to produce the host molecule,
both starting from commercially available compounds and resulting in low but usable yields. Structural and functional characterization was performed using DFT-based molecular modelling and
fluorescence titrations. These studies confirmed selective binding
of oligoamines, with spermine and spermidine forming the most
stable complexes.
Both the modelling and the titration experiments revealed sequential 1:1 and 1:2 host–guest complex formation. Binding constants
and cooperativity effects were calculated using global non-linear
regression of the titration data. Spermine showed strong binding
and negative cooperativity which made it the preferred analogue
for coordination, while spermidine exhibited the highest overall
stability in binding but no cooperativity effect. The receptor’s molecular recognition behaviour suggests potential for use in bioimaging, diagnostics, or targeted drug delivery applications—particularly in cancer research.