In a study published in Frontiers in Chemistry, Bader Huwaimel and colleagues employed density functional theory (DFT) to systematically compare how rolicyclidine—abbreviated Php in their work—interacts with pristine C60 fullerene and two substitutionally doped derivatives: boron-doped BC59 and silicon-doped SiC59. The goal was to identify which of these spherical carbon nanocages could serve as the foundation for a next-generation electrochemical sensor capable of detecting the dissociative drug quickly, accurately, and reversibly. The research represents a pre-synthesis computational screening designed to narrow candidates before any material is fabricated in the laboratory.

The computational framework was carefully constructed to ensure robustness. All geometries were optimized in the water phase using the B97D/6-31G(d) level of theory with the CPCM solvation model, a choice made because rolicyclidine detection may ultimately be performed in aqueous biological or forensic matrices. The B97D functional was selected specifically because it includes Grimme’s empirical dispersion correction, making it well suited for fullerene-based adsorption systems where dispersion forces, π-π contacts, van der Waals interactions, and weak donor-acceptor contacts dominate. To guard against basis-set artifacts, the team repeated all key calculations at the larger B97D/6-311G(d,p) level and independently validated trends using the range-separated hybrid functional ωB97XD/6-31G(d). Frequency calculations confirmed that every optimized structure represented a true minimum rather than a transition state.

Structural analysis revealed that doping fundamentally reshapes the fullerene cage. In pristine C60, carbon-carbon bond lengths of 1.404 to 1.455 Å and bond angles spanning 108° to 120° reflect the intrinsic curvature of a predominantly sp2-hybridized carbon network. When boron replaces a carbon atom, B-C bonds elongate slightly to 1.533–1.555 Å with mild angular compression, preserving the fundamental electronic character of the cage while introducing a controlled local distortion. Silicon doping, by contrast, produces the most dramatic structural change: Si-C bonds stretch to 1.81–1.86 Å and bond angles compress to between 90.37° and 99.47°, signaling a shift from sp2 toward a more sp3-like hybridization around the dopant. This pronounced pyramidalization locally disrupts the π-network and creates a highly reactive site.

The calculated infrared spectrum of pristine C60 showed excellent agreement with experimental data, reproducing the four characteristic IR-active modes near 1,428, 1,183, 577, and 528 cm−1 with only small frequency deviations typical of harmonic DFT calculations. For the doped structures, the spectra exhibited a clear increase in the number of active bands, a direct consequence of symmetry breaking that activates additional vibrational modes. Molecular electrostatic potential (MEP) maps further illuminated the interaction chemistry: while pristine C60 displayed a uniformly electron-deficient surface, the boron and silicon dopant atoms emerged as the most electrophilic centers. For rolicyclidine, the electron-rich nitrogen atom stood out as the primary nucleophilic site, suggesting that the drug’s pyrrolidine nitrogen would preferentially engage the dopant atoms in the modified cages.

The electronic reactivity parameters told a compelling story about sensing potential. At the B97D/6-31G(d) level, the HOMO-LUMO gap of pristine C60 was 1.67 eV—numerically close to reported experimental values of approximately 1.5–1.86 eV. Boron and silicon substitution reduced this gap to 1.35 eV and 1.18 eV, respectively. Upon rolicyclidine adsorption, the gaps narrowed further to 0.85, 0.40, and 0.98 eV for C60@Php, BC59@Php, and SiC59@Php. Among the complexes, BC59@Php exhibited the strongest electronic perturbation, with the smallest gap, the highest softness and maximum charge-transfer descriptor values, and a large negative electrophilicity-based charge-transfer value of −12.64, indicating pronounced electron donation from the drug toward the electron-deficient boron site. Because electrical conductivity depends exponentially on the band gap, this approximately 70 percent gap reduction in BC59@Php yields the largest relative change in the gap-derived conductivity descriptor among the studied complexes.

Dipole moment calculations added another layer of insight. Pristine C60 carries a dipole moment of exactly zero, consistent with its highly symmetric icosahedral structure. Upon rolicyclidine adsorption, this jumped to 4.86 Debye. The isolated BC59 structure already displayed a nonzero dipole moment of 1.50 Debye due to the asymmetry introduced by heteroatom substitution, rising to 6.66 Debye upon complexation. The most dramatic effect, however, belonged to the silicon-doped cage: isolated SiC59 had a modest dipole moment of 0.35 Debye, but after rolicyclidine adsorption it surged to 21.86 Debye—an approximately 62-fold increase that signifies exceptionally strong electronic perturbation and charge separation within the complex. Both the B97D and ωB97XD functionals predicted the same qualitative ordering: SiC59@Php > BC59@Php > C60@Php.

The adsorption energy results revealed a fundamental distinction between capture and sensing. At the B97D/6-31G(d) level with BSSE correction, the adsorption energies were −6.96, −8.04, and −38.79 kcal·mol−1 for C60@Php, BC59@Php, and SiC59@Php, respectively. Corresponding recovery-time estimates were 1.28 × 10−7, 7.97 × 10−7, and 2.81 × 1016 seconds. While C60@Php and BC59@Php are predicted to undergo rapid desorption—ideal for a reusable sensor—the astronomically long recovery time of SiC59@Php indicates nearly irreversible adsorption. The ωB97XD calculations reproduced the same qualitative ordering, and additional single-point calculations using a physiological-saline-like dielectric constant of εr = 76.2 changed the adsorption energies by only 0.01 to 0.05 kcal·mol−1, confirming that the principal conclusions are insensitive to small changes in the bulk dielectric constant.

Noncovalent Interaction (NCI) and Reduced Density Gradient (RDG) analyses, together with Electron Localization Function (ELF) and Localized Orbital Locator (LOL) maps, provided qualitative visualization of the interaction mechanisms. For C60@Php, the interfacial region was dominated by green isosurfaces consistent with dispersive and van der Waals contributions. BC59@Php revealed a localized blue attractive region near the boron-containing interaction site and the nitrogen-containing part of the drug, consistent with a localized donor-acceptor contribution. SiC59@Php exhibited both attractive blue regions near the silicon site and extensive green dispersive regions over the contact area, with elevated ELF values exceeding 0.85 in the contact zone—features qualitatively consistent with substantially stronger and more strongly polarized interaction than those predicted for the other complexes.

Based on this comparative theoretical screening, the researchers propose an application-dependent distinction: BC59 may be prioritized for experimental sensing evaluation because it combines rapid predicted recovery with the largest relative electronic perturbation, whereas SiC59 may be prioritized for strong adsorption or removal studies given its substantially more negative corrected adsorption energy and extremely slow predicted desorption. The team outlines concrete experimental validation routes, including synthesis of doped fullerenes via arc discharge or chemical vapor deposition, electrode fabrication on glassy carbon or gold substrates, electrochemical characterization using cyclic voltammetry and impedance spectroscopy, and selectivity testing against structurally related interferents. The authors caution that these assignments remain theoretical screening results requiring validation through material fabrication, kinetic measurements, and evaluation under realistic operating conditions—but the computational evidence now points clearly toward two distinct buckyball candidates, each optimized for a different role in the fight against rolicyclidine misuse.

Subject of Research: DFT screening of boron- and silicon-doped C60 fullerenes identifies BC59 as a candidate reversible sensor and SiC59 as a strong adsorbent for rolicyclidine detection.

Article Title: Theoretical insights into rolicyclidine adsorption and sensing using modified C60 fullerene

Article References: Huwaimel, B., Alqarni, S., Alghubayshi, A., Alotaibi, T., Alsaab, H. O., Alzhrani, R. M., & Abouzied, A. S. (2026). Theoretical insights into rolicyclidine adsorption and sensing using modified C60 fullerene. Frontiers in Chemistry, 14, Article 1908245. https://doi.org/10.3389/fchem.2026.1908245

Image Credits: AI Generated

DOI: 10.3389/fchem.2026.1908245

Keywords: rolicyclidine, C60 fullerene, boron doping, silicon doping, DFT, drug detection, electrochemical sensor, adsorption energy, HOMO-LUMO gap, BC59, SiC59, forensic toxicology