Posted by Polycyclic aromatic hydrocarbons (PAHs) are widespread combustion-derived pollutants, and 1-hydroxypyrene (1HOPy) is the standard biomarker used to track human exposure to them. Current gold-standard methods (HPLC- or LC-MS/MS-based) are sensitive but require lab infrastructure, sample pre-treatment and skilled operators, which limits field-deployable or point-of-care testing.
In this study, six CD-based platforms — the monomers HPβCD, βCD and γCD, epichlorohydrin-crosslinked polymers pβCD and pγCD, and two synthetic βCD dimers linked at either the secondary (βDim1) or primary (βDim2) rim — were screened for their ability to bind 1HOPy and modulate its intrinsic fluorescence. Using UV-Vis absorption, steady-state and time-resolved fluorescence, and multivariate global analysis of the titration data, distinct binding stoichiometries (1:1, 2:1 and 2:2) were found with affinities spanning 10³-10⁵ M⁻¹, cross-checked by molecular dynamics (MD) and thermodynamic-integration free-energy calculations.
HPβCD showed the tightest 1:1 binding (K ≈ 1.0 × 10⁵ M⁻¹) but only modest spectral changes. γCD instead assembled cooperatively into 2:2 complexes that sandwich two 1HOPy molecules together, switching on a distinctive excimer emission at 480 nm — a compact, MD-confirmed architecture stabilized by π–π stacking. However, the most interesting result came from βDim2: complexation triggered ground-state deprotonation of 1HOPy, generating a phenolate species with its own diagnostic emission, distinguishable from both free 1HOPy and related PAH metabolites. A detailed computational analysis reasonably reproduced the experimental affinity hierarchy, also suggesting the positively polarized ammonium/thiourea linker of βDim2 as a favourable pocket for stabilizing the phenolate together with the surrounding hydrogen-bond network.
These results make βDim2 the most promising candidate for real-world 1OHPy sensing: selective excitation of the phenolate allowed linear detection of 1HOPy at biological relevant concentrations, from 10 to 1000 nM, with no interference from structurally related metabolites or parent pyrene itself. The dimer also carries a BOC-protected amine, offering a straightforward handle for grafting onto sensing surfaces, a following step toward electrochemical or hybrid optical/electrochemical devices.
Tailoring cyclodextrin platforms for nanomolar range fluorescence detection of 1-hydroxypyrene as biomarker of polycyclic aromatic hydrocarbons – D. Veclani , M. Agnes , C.F. Mautone , J. Ortigosa , C. Modenutti , M. Malanga , J. M. Garcia Fernandez , J.M. Benito , I. Manet , Journal of Molecular Structure 2026, https://doi.org/10.1016/j.molstruc.2026.147579
Preprint SSRN: https://ssrn.com/abstract=6886886 or http://dx.doi.org/10.2139/ssrn.6886886
Preprint ChemRxiv: https://doi.org/10.26434/chemrxiv-2026-kjpmp/v2