Akalanka B. Ekanayake

Here we investigate the effects of crystal size on the mechanical properties (Young’s modulus, framework flexibility) of a switchable metal–organic framework (MOF): zeolitic imidazolate framework-90 (ZIF-90) individual crystals with sizes ranging from micro- to nanodimensions. Atomic force microscopy (AFM) nanoindentation measurements over individual crystals reveal a significant reduction in Young’s modulus with crystal-size reduction that follows a continuous power-law relationship, where Young’s modulus decreases by nearly 1 order of magnitude as crystal base size decreases from ∼5 to 0.4 μm. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) analyses coupled with the AFM results reveal that the origin of the size-dependent framework flexibility is primarily attributed to an increased concentration of missing metal node defects for smaller crystals. The presence of missing metal node defects in ZIF-90 crystals was further confirmed by single-crystal optical photothermal infrared spectroscopy measurements. Significantly, the value of the power-law exponent in Young’s modulus versus crystal-size data was related to the magnitude of the relative increase in the number of missing metal node defects, indicating that the extent of the framework flexibility change with crystal size can in part be attributed to the rate of defect accumulation with crystal downsizing at the nanoscale. These findings indicate that the power-law scaling of mechanical properties may serve as an approach to assess the size-dependent extent of point-defect evolution in switchable MOFs, potentially enabling a rational design of solids with controlled functional properties.

A rock tumbler outfitted with LED lights allows for mechanochemical preparation of photoactive cocrystals.

Radiation therapy is a standard of care treatment for patients with glioblastoma. However, patients’ survival rate is dismal, with nearly all patients experiencing disease progression after treatment. Enriched iron content associated with increased transferrin receptor (TfR) expression is an indicator of poor glioblastoma patient outcomes; however, the underlying contributions to tumor progression remain elusive. The goal of this present study is to understand how iron metabolism in glioma contributes to radiation-induced glioblastoma cell motility. U251 and a doxycycline-inducible ferritin heavy chain overexpressing U251 (U251 FtH⁺) cell line were used. For in vitro studies, cells were irradiated with 2 Gy using a ³⁷Cs source, and after 72 h, atomic force microscopy (AFM) nanoindentation was employed to assess changes in cell stiffness following irradiation. Cell motility was studied using temporal confocal microscopy. For in vivo studies, U251 cells were grown in the rear flanks of female nude athymic mice, and the tumor was irradiated with five fractions of 2 Gy (10 Gy). The tumors were then imaged using a GE 7T small animal MRI to assess changes in T2* MRI, and colorimetric analysis of labile iron was performed using ferrozine. Following irradiation, a biomechanical shift characterized by decreased cell stiffness along with increased cell motility occurred in U251 cells, which corresponded to increased TfR expression. FtH overexpression completely reversed the enhanced cell motility following irradiation. Irradiation of U251 tumors induced the same iron metabolic shift. Interestingly, the change in labile iron in U251 tumors corresponded with an increase in T2* relaxation times, suggesting that T2* mapping may serve as a surrogate marker for assessing radiation-induced changes in iron metabolism.

Reducing crystal size in ZIF-7 MOFs leads to significantly increased framework flexibility with smaller crystals exhibiting more point defects and lower metal content. Such size-dependent behaviour may enable rational design of various materials.

Cyclometallated Pt(II) complexes possessing hydrophobic 2-phenylpyridine (ppy) ligands and hydrophilic acetonylacetone (acac) ligands have been investigated for their ability to detect amyloid fibrils via luminescence response. Using hen egg-white lysozyme (HEWL) as a model amyloid protein, Pt(II) complexes featuring benzanilide-substituted ppy ligands and ethylene glycol-functionalized acac ligands demonstrated enhanced luminescence in the presence of HEWL fibrils, whereas Pt(II) complexes lacking complementary hydrophobic/hydrophilic ligand sets displayed little to no emission enhancement. An amphiphilic Pt(II) complex incorporating a bis(ethylene glycol)-derivatized acac ligand was additionally found to trigger restructuring of HEWL fibrils into smaller spherical aggregates. Amphiphilic Pt(II) complexes were generally non-toxic to SH-SY5Y neuroblastoma cells, and several complexes also exhibited enhanced luminescence in the presence of Aβ₄₂ fibrils associated with Alzheimer's disease. This study demonstrates that easily prepared and robust (ppy)Pt^II(acac) complexes show promising reactivity toward amyloid fibrils and represent attractive molecular scaffolds for design of small-molecule probes targeting amyloid assemblies.