Synthesis and Water Solubility of Adamantyl-OEG-fullerene Hybrids

A series of new adamantyl-oligoethyleneglycol-fullerene hybrids was prepared via Bingel−Hirsch functionalization of the C60 fullerene with various adamantyl-oligoethyleneglycol malonates. As NMDA-targeted antioxidants, these compounds may have the potential to be developed as therapeutic agents for the treatment of neurological disorders

Diffusion ¹⁹F‑NMR of Nanofluorides: In Situ Quantification of Colloidal Diameters and Protein Corona Formation in Solution

The NMR-detectability of elements of organic ligands that stabilize colloidal inorganic nanocrystals (NCs) allow the study of their diffusion characteristics in solutions. Nevertheless, these measurements are sensitive to dynamic ligand exchange and often lead to overestimation of diffusion coefficients of dispersed colloids. Here, we present an approach for the quantitative assessment of the diffusion properties of colloidal NCs based on the NMR signals of the elements of their inorganic cores. Benefiting from the robust 19F-NMR signals of the fluorides in the core of colloidal CaF2 and SrF2, we show the immunity of 19F-diffusion NMR to dynamic ligand exchange and, thus, the ability to quantify, with high accuracy, the colloidal diameters of different types of nanofluorides in situ. With the demonstrated ability to characterize the formation of protein corona at the surface of nanofluorides, we envision that this study can be extended to additional formulations and applications

Paramagnetic MgF₂ Nanocrystals for ¹⁹F Magnetic Resonance Imaging

MgF2-based formulations have unique physicochemical properties, making them attractive for diverse applications. Here, we show the ability to control the morphology of Sm3+-doped, paramagnetic MgF2 nanocrystals (Sm:MgF2 NCs) for use as nanosized imaging agents for 19F-magnetic resonance imaging (19F-MRI). By reducing the temperature of the reaction mixture from 160 to 110 °C and shortening the reaction time from 16 to 3 h, the morphology of the fabricated oleate-coated Sm:MgF2 NCs was transitioned from rod-shaped to spherical-shaped nanofluorides, both with a characteristic high-resolution liquid-state 19F-NMR resonance at −198 ppm. Further coating the surface of the spheric Sm:MgF2 NCs with a phospholipid layer resulted in a water-soluble formulation that was used to show its detectability with 19F-MRI

Cooperative Doping in Ultrasmall BaF₂ Nanocrystals for Multimodal ¹⁹F‑MRI and CT Applications

Nanostructured metal fluorides (nanofluorides) are an emerging type of inorganic nanocrystals (NCs) with unique physiochemical properties for advanced applications. One recent demonstration used water-dispersed ultrasmall CaF2 nanofluorides as imaging agents that combined the advantages of inorganic NCs with the benefit of background-free 19F-magnetic resonance imaging (19F-MRI). Nevertheless, obtaining small nanofluorides with a face-centered cubic crystal structure, where all fluorides are magnetically equivalent to result in a single 19F NMR signal, is challenging for other types of nanofluorides, preventing their use in 19F-MRI. Here, we show the development of ultrasmall, water-dispersed, barium fluoride (BaF2) NCs for bioimaging applications. By doping BaF2 with two types of lanthanides, diamagnetic-La3+ and paramagnetic-Sm3+, we were able to control the morphology and 19F-MR properties of the final La,Sm:BaF2 (termed LaSamBa) formulation. The fine-tuning of the La3+ content enabled us to obtain monodispersed 4.5 nm NCs, and control over the Sm3+ content provided LaSamBa with very short T1 relaxation properties (ca. 100 ms) needed for enhanced 19F-MRI sensitivity. This type of nanofluorides was examined in two different imaging modalities (i.e., 19F-MRI and CT), benefiting from their single 19F-NMR signal and the high atomic number of barium atoms, respectively. As their 19F chemical shift significantly differs from that of other nanofluorides (e.g., CaF2 and SrF2), LaSamBa expanded the nanofluoride library for future multitarget 19F-MRI studies

Cation-Ligand Complexation Mediates the Temporal Evolution of Colloidal Fluoride Nanocrystals through Transient Aggregation

Colloidal inorganic nanofluorides have aroused great interest for various applications with their development greatly accelerated thanks to advanced synthetic approaches. Nevertheless, understanding their colloidal evolution and the factors that affect their dispersion could improve the ability to rationally design them. Here, using a multimodal in situ approach that combines DLS, NMR, and cryogenic-TEM, we elucidate the formation dynamics of nanofluorides in water through a transient aggregative phase. Specifically, we demonstrate that ligand-cation interactions mediate a transient aggregation of as-formed CaF2 nanocrystals (NCs) which governs the kinetics of the colloids’ evolution. These observations shed light on key stages through which CaF2 NCs are dispersed in water, highlighting fundamental aspects of nanofluorides formation mechanisms. Our findings emphasize the roles of ligands in NCs’ synthesis beyond their function as surfactants, including their ability to mediate colloidal evolution by complexing cationic precursors, and should be considered in the design of other types of NCs

Cation-Ligand Complexation Mediates the Temporal Evolution of Colloidal Fluoride Nanocrystals through Transient Aggregation

Colloidal inorganic nanofluorides have aroused great interest for various applications with their development greatly accelerated thanks to advanced synthetic approaches. Nevertheless, understanding their colloidal evolution and the factors that affect their dispersion could improve the ability to rationally design them. Here, using a multimodal in situ approach that combines DLS, NMR, and cryogenic-TEM, we elucidate the formation dynamics of nanofluorides in water through a transient aggregative phase. Specifically, we demonstrate that ligand-cation interactions mediate a transient aggregation of as-formed CaF2 nanocrystals (NCs) which governs the kinetics of the colloids’ evolution. These observations shed light on key stages through which CaF2 NCs are dispersed in water, highlighting fundamental aspects of nanofluorides formation mechanisms. Our findings emphasize the roles of ligands in NCs’ synthesis beyond their function as surfactants, including their ability to mediate colloidal evolution by complexing cationic precursors, and should be considered in the design of other types of NCs

Cation-Ligand Complexation Mediates the Temporal Evolution of Colloidal Fluoride Nanocrystals through Transient Aggregation

Colloidal inorganic nanofluorides have aroused great interest for various applications with their development greatly accelerated thanks to advanced synthetic approaches. Nevertheless, understanding their colloidal evolution and the factors that affect their dispersion could improve the ability to rationally design them. Here, using a multimodal in situ approach that combines DLS, NMR, and cryogenic-TEM, we elucidate the formation dynamics of nanofluorides in water through a transient aggregative phase. Specifically, we demonstrate that ligand-cation interactions mediate a transient aggregation of as-formed CaF2 nanocrystals (NCs) which governs the kinetics of the colloids’ evolution. These observations shed light on key stages through which CaF2 NCs are dispersed in water, highlighting fundamental aspects of nanofluorides formation mechanisms. Our findings emphasize the roles of ligands in NCs’ synthesis beyond their function as surfactants, including their ability to mediate colloidal evolution by complexing cationic precursors, and should be considered in the design of other types of NCs

Single ¹⁹F Probe for Simultaneous Detection of Multiple Metal Ions Using miCEST MRI

The local presence and concentration of metal ions in biological systems has been extensively studied <i>ex vivo</i> using fluorescent dyes. However, the detection of multiple metal ions <i>in vivo</i> remains a major challenge. We present a magnetic resonance imaging (MRI)-based method for noninvasive detection of specific ions that may be coexisting, using the tetrafluorinated derivative of the BAPTA (TF-BAPTA) chelate as a ¹⁹F chelate analogue of existing optical dyes. Taking advantage of the difference in the ion-specific ¹⁹F nuclear magnetic resonance (NMR) chemical shift offset (Δω) values between the ion-bound and free TF-BAPTA, we exploited the dynamic exchange between ion-bound and free TF-BAPTA to obtain MRI contrast with multi-ion chemical exchange saturation transfer (miCEST). We demonstrate that TF-BAPTA as a prototype single ¹⁹F probe can be used to separately visualize mixed Zn²⁺ and Fe²⁺ ions in a specific and simultaneous fashion, without interference from potential competitive ions

Cation-Ligand Complexation Mediates the Temporal Evolution of Colloidal Fluoride Nanocrystals through Transient Aggregation

Colloidal inorganic nanofluorides have aroused great interest for various applications with their development greatly accelerated thanks to advanced synthetic approaches. Nevertheless, understanding their colloidal evolution and the factors that affect their dispersion could improve the ability to rationally design them. Here, using a multimodal in situ approach that combines DLS, NMR, and cryogenic-TEM, we elucidate the formation dynamics of nanofluorides in water through a transient aggregative phase. Specifically, we demonstrate that ligand-cation interactions mediate a transient aggregation of as-formed CaF2 nanocrystals (NCs) which governs the kinetics of the colloids’ evolution. These observations shed light on key stages through which CaF2 NCs are dispersed in water, highlighting fundamental aspects of nanofluorides formation mechanisms. Our findings emphasize the roles of ligands in NCs’ synthesis beyond their function as surfactants, including their ability to mediate colloidal evolution by complexing cationic precursors, and should be considered in the design of other types of NCs

Metal Ion Sensing Using Ion Chemical Exchange Saturation Transfer ¹⁹F Magnetic Resonance Imaging

Although metal ions are involved in a myriad of biological processes, noninvasive detection of free metal ions in deep tissue remains a formidable challenge. We present an approach for specific sensing of the presence of Ca²⁺ in which the amplification strategy of chemical exchange saturation transfer (CEST) is combined with the broad range of chemical shifts found in ¹⁹F NMR spectroscopy to obtain magnetic resonance images of Ca²⁺. We exploited the chemical shift change (Δω) of ¹⁹F upon binding of Ca²⁺ to the 5,5′-difluoro derivative of 1,2-bis­(<i>o</i>-amino­phenoxy)­ethane-<i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-tetra­acetic acid (5F-BAPTA) by radiofrequency labeling at the Ca²⁺-bound ¹⁹F frequency and detection of the label transfer to the Ca²⁺-free ¹⁹F frequency. Through the substrate binding kinetics we were able to amplify the signal of Ca²⁺ onto free 5F-BAPTA and thus indirectly detect low Ca²⁺ concentrations with high sensitivity