Sulfur quantum dots (SQDs) have gained significant attention due to their tunable photoluminescence, high photostability, and low toxicity, offering an eco-friendly alternative to heavy-metal-based QDs. However, their application as independent sensory platforms is limited by the absence of intrinsic receptor groups.

This study presents a novel synthesis of SQDs using decasubstituted amide- and amino-functionalized pillar[5]arenes (P[5]As), addressing three key challenges. Firstly, the P[5]As act as effective surface passivation agents. The high density of electron-donating amino groups ensures their stable anchoring to the SQD surface, suppressing defect formation and aggregation. Secondly, these amino groups generate an alkaline medium necessary for sulfur dissolution and nanoparticle formation, eliminating the need for traditionally used NaOH in SQD synthesis, thereby reducing the number of reagents. Finally, P[5]As are capable of forming host–guest inclusion complexes, which imparts molecular recognition functionality to the SQDs. The sensory potential of the resulting nanomaterials was evaluated by studying their interaction with a series of antitumor drugs (tegafur, floxuridine, 5-fluorouracil, dacarbazine, and lomustine).

The following methods were applied to achieve the goal: NMR, IR, UV-vis, and fluorescence spectroscopy; MALDI-TOF mass spectrometry; elemental analysis; DLS; and TEM.

For the first time, SQDs were synthesized in the presence of P[5]As, serving as both surface passivation agents and alkaline medium providers. The resulting P[5]As-SQDs exhibit high-intensity blue fluorescence, average sizes of up to 10 nm, and a spherical morphology. UV-vis spectroscopy demonstrated the selective binding of 5-fluorouracil to the P[5]As-SQDs, confirming the key role of the macrocyclic ligand in recognition. Binding constants (lgK_as) determined by UV-vis and fluorescence titration were 2.42 and 2.06, respectively.

Thus, functionalization with amide- and amino-functionalized P[5]As provides a validated single-step strategy to create stable, recognition-capable SQDs. This approach opens promising avenues for developing SQD-based sensors, particularly for detecting specific bioactive molecules such as 5-fluorouracil.