We report on the encapsulation of the antibiotic clofazimine (CLZ) within the pores of mesoporous silica particles having hydrophilic (C_BET value of 137) and more hydrophobic (C_BET value of 94 after calcination at 600 °C) surfaces. We studied the effect of pH on the released amount of CLZ in aqueous solutions and observed a maximum at pH 4.1 in correlation with the solubility of the drug. Less release of the drug was observed from the more hydrophobic particles which was attributed to a difference in the affinity of the drug to the carrier particles. Fluorescence lifetime imaging microscopy, emission spectra, and fluorescence lifetimes of single drug loaded particles provided detailed understanding and new knowledge of the physical form of the encapsulated drug and the distribution within the particles. The distribution of CLZ within the particles was independent of the surface chemistry of the particles. The confirmation of CLZ molecules as monomers or aggregates was revealed by controlled removal of the drug with solvent. Additionally, the observed optical “halo effect” in the fluorescent images was interpreted in terms of specific quenching of high concentration of molecules. The emission lifetime experiments suggest stronger interaction of CLZ with the more hydrophobic particles, which is relevant to its release. The results reported in this work demonstrate that tuning the hydrophilicity/hydrophobicity of mesoporous silica particles can be used as a tool to control the release without impacting their loading ability.

Clofazimine (CLZ) is an effective antibiotic used against a wide spectrum of Gram-positive bacteria and leprosy. One of its main drawbacks is its poor solubility in water. Silica based materials are used as drug delivery carriers that can increase the solubility of different hydrophobic drugs. Here, we studied how the properties of the silica framework of the mesoporous materials SBA-15, MCM-41, Al-MCM-41, and zeolites NaX, NaY, and HY affect the loading, stability, and distribution of encapsulated CLZ. Time-correlated single-photon counting (TCSPC) and fluorescence lifetime imaging microscopy (FLIM) experiments show the presence of neutral and protonated CLZ (1.3–3.8 ns) and weakly interacting aggregates (0.4–0.9 ns), along with H- and J-type aggregates (<0.1 ns). For the mesoporous and HY zeolite composites, the relative contribution to the overall emission spectra from H-type aggregates is low (<10%), while for the J-type aggregates it becomes higher (~30%). For NaX and NaY the former increased whereas the latter decreased. Although the CLZ@mesoporous composites show higher loading compared to the CLZ@zeolites ones, the behavior of CLZ is not uniform and its dynamics are more heterogeneous across different single mesoporous particles. These results may have implication in the design of silica-based drug carriers for better loading and release mechanisms of hydrophobic drugs.

The design of improved organic linkers for the further engineering of smarter metal–organic framework (MOF) materials has become a paramount task for a wide number of material scientists. In this report, a luminescent double-functionalized push–pull (electron donor–acceptor) archetype organic molecule, dimethyl 4-amino-8-cyanonaphthalene-2,6-dicarboxylate (Me₂CANADC), has been synthesized and characterized. The optical steady-state properties of Me₂CANADC are strongly influenced by the surrounding environment as a direct consequence of its strong charge transfer (CT) character. The relaxation from its first electronically excited singlet state follows a double pathway: (1) on one side deactivating from its local excited (LE) state in the sub-picosecond or picosecond time domain, and (2) on the other side undergoing an ultrafast intramolecular charge transfer (ICT) reaction that is slowing down in viscous solvents. The deactivation to the ground state of these species with CT character is the origin of the Me₂CANADC luminescence, and they present solvent-dependent lifetime values ranging from 8 to 18 ns. The slow photodynamics of Me₂CANADC unveils the coexistence of a non-emissive triplet excited state and the formation of a long-lived charge separated state (2 µs). These observations highlight the promising optical properties of Me₂CANADC linker, opening a window for the design of new functional MOFs with huge potential to be applied in the fields of luminescent sensing and optoelectronics.

Rifampicin (Rif) is an effective antibiotic against mycobacterial infections and a wide range of Gram-positive and Gram-negative bacteria. The geometry, conformation and the intramolecular H-bond network of Rif can affect its antibacterial efficiency. In this work, we report on the excited-state dynamics of Rif in sodium phosphate buffer and dichloromethane solutions using femtosecond time-resolved spectroscopic methods. The femtosecond UV-Vis-nearIR transient absorption and fluorescence up-conversion experiments reveal an ultrafast (<100 fs) Franck–Condon relaxation with a partial charge transfer character in S₁, and a short-lived emission (τ ∼ 6 ps) due to a non-radiative relaxation to the ground state, associated with the stretching of the vibrational mode of the Rif internal H-bond network. The large Stokes-shifted emission (∼6800 cm⁻¹) indicates a significant electronic change in the excited-state. In deuterated potassium phosphate buffer, the decay time becomes longer (∼20 ps). The large kinetic isotope effect (KIE) of ∼4 on the decay rate indicates that the stretching modes of the internal H-bond network are slowed by the H/D isotope substitution. The results provide new information on the dynamics of Rif structures and the related processes in aqueous solutions, showing that the internal H-bonding interactions are the ones that govern the ground and excited state properties of Rif but water molecules exert additional stabilization of its zwitterionic form through intermolecular H-bonds, which is responsible for its high antimicrobial activity.