Minimal Self-Immolative Probe for Multimodal Fluoride Detection

Two single-molecule, self-immolative fluoride probes, namely <i>tert</i>-butyldimethylsilyl-protected 2- and 4-difluoromethylphenol, are described. Compared to similar systems previously described, the probes are characterized by a simpler structure and straightforward, two-step preparation. Nevertheless, they allow the detection of fluoride ions at micromolar concentration by the naked eye, UV–vis absorption, and fluorescence. A detailed investigation of the self-immolative reaction reveals that the rate-limiting step is the release of the first fluoride ion from the difluoromethylphenolate intermediate. Moreover, the mutual position of the difluoromethyl- and <i>tert</i>-butyldimethylsilyl-protected residues has a relevant effect on the reactivity. Likely, a CF₂H–O hydrogen bond in the 2-isomer increases the reactivity of the silyl ether toward hydrolytic cleavage but also stabilizes the phenolate intermediate, slowing the release of fluoride ions

Efficient Phosphodiester Cleaving Nanozymes Resulting from Multivalency and Local Medium Polarity Control

The self-organization of Zn­(II) complexes on the surface of 1.6-nm diameter gold nanoparticles (nanozymes) allows the spontaneous formation of multiple bimetallic catalytic sites capable to promote the cleavage of a RNA model substrate. We show that by tuning the structure of the nanoparticle-coating monolayer, it is possible to decrease the polarity of the reaction site, and this in turn generates remarkable increments of the cleavage efficiency

Turning Supramolecular Receptors into Chemosensors by Nanoparticle-Assisted “NMR Chemosensing”

By exploiting a magnetization transfer between monolayer-protected nanoparticles and interacting analytes, the NMR chemosensing protocol provides a general approach to convert supramolecular receptors into chemosensors via their conjugation with nanoparticles. In this context, the nanoparticles provide the supramolecular receptor not only with the “bulkiness” necessary for the NMR chemosensing approach but also with a different selectivity as compared to the parent receptor. We here demonstrate that gold nanoparticles of 1.8 nm core coated with a monolayer of 18-crown-6 ether derivatives can detect and identify protonated primary amines in methanol and in water, and even discriminate between two biogenic diamines that are selectively detected over monoamines and α-amino acids

Lanthanide-Based NMR: A Tool To Investigate Component Distribution in Mixed-Monolayer-Protected Nanoparticles

Gd³⁺ ions, once bound to the monolayer of organic molecules coating the surface of gold nanoparticles, produce a paramagnetic relaxation enhancement (PRE) that broadens and eventually cancels the signals of the nuclear spins located nearby (within 1.6 nm distance). In the case of nanoparticles coated with mixed monolayers, the signals arising from the different coating molecules experience different PRE, depending on their distance from the binding site. As a consequence, observation of the signal broadening patterns provides direct information on the monolayer organization

Nanoparticle-Assisted NMR Detection of Organic Anions: From Chemosensing to Chromatography

Monolayer-protected nanoparticles provide a straightforward access to self-organized receptors that selectively bind different substrates in water. Molecules featuring different kinds of noncovalent interactions (namely, hydrophobic, ion pairing, and metal–ligand coordination) can be grafted on the nanoparticle surface to provide tailored binding sites for virtually any class of substrate. Not only the selectivity but also the strength of these interactions can be modulated. Such recognition ability can be exploited with new sensing protocols, based on NMR magnetization transfer and diffusion-ordered spectroscopy (DOSY), to detect and identify organic molecules in complex mixtures

Data_Sheet_1_Selective Targeting of Proteins by Hybrid Polyoxometalates: Interaction Between a Bis-Biotinylated Hybrid Conjugate and Avidin.docx

<p>The Keggin-type polyoxometalate [γ-SiW₁₀O₃₆]⁸⁻ was covalently modified to obtain a bis-biotinylated conjugate able to bind avidin. Spectroscopic studies such as UV-vis, fluorimetry, circular dichroism, coupled to surface plasmon resonance technique were used to highlight the unique interplay of supramolecular interactions between the homotetrameric protein and the bis-functionalized polyanion. In particular, the dual recognition mechanism of the avidin encompasses (i) a complementary electrostatic association between the anionic surface of the polyoxotungstate and each positively charged avidin subunit and (ii) specific host-guest interactions between each biotinylated arm and a corresponding pocket on the tetramer subunits. The assembly exhibits peroxidase-like reactivity and it was used in aqueous solution for L-methionine methyl ester oxidation by H₂O₂. The recognition phenomenon was then exploited for the preparation of layer-by-layer films, whose structural evolution was monitored in situ by ATR-FTIR spectroscopy. Finally, cell tracking studies were performed by exploiting the specific interactions with a labeled streptavidin.</p

C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes

Poly­(2-methyl-2-oxazoline) (PMOXA) is an alternative promising polymer to poly­(ethylene glycol) (PEG) for design and engineering of macrophage-evading nanoparticles (NPs). Although PMOXA-engineered NPs have shown comparable pharmacokinetics and <i>in vivo</i> performance to PEGylated stealth NPs in the murine model, its interaction with elements of the human innate immune system has not been studied. From a translational angle, we studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived organically modified silica NPs (PMOXA-coated NPs) of approximately 100 nm in diameter with human complement system, blood leukocytes, and macrophages and compared their performance with PEGylated and uncoated NP counterparts. Through detailed immunological and proteomic profiling, we show that PMOXA-coated NPs extensively trigger complement activation in human sera exclusively through the classical pathway. Complement activation is initiated by the sensing molecule C1q, where C1q binds with high affinity (<i>K</i>_d = 11 ± 1 nM) to NP surfaces independent of immunoglobulin binding. C1q-mediated complement activation accelerates PMOXA opsonization with the third complement protein (C3) through the amplification loop of the alternative pathway. This promoted NP recognition by human blood leukocytes and monocyte-derived macrophages. The macrophage capture of PMOXA-coated NPs correlates with sera donor variability in complement activation and opsonization but not with other major corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps

C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes

Poly­(2-methyl-2-oxazoline) (PMOXA) is an alternative promising polymer to poly­(ethylene glycol) (PEG) for design and engineering of macrophage-evading nanoparticles (NPs). Although PMOXA-engineered NPs have shown comparable pharmacokinetics and <i>in vivo</i> performance to PEGylated stealth NPs in the murine model, its interaction with elements of the human innate immune system has not been studied. From a translational angle, we studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived organically modified silica NPs (PMOXA-coated NPs) of approximately 100 nm in diameter with human complement system, blood leukocytes, and macrophages and compared their performance with PEGylated and uncoated NP counterparts. Through detailed immunological and proteomic profiling, we show that PMOXA-coated NPs extensively trigger complement activation in human sera exclusively through the classical pathway. Complement activation is initiated by the sensing molecule C1q, where C1q binds with high affinity (<i>K</i>_d = 11 ± 1 nM) to NP surfaces independent of immunoglobulin binding. C1q-mediated complement activation accelerates PMOXA opsonization with the third complement protein (C3) through the amplification loop of the alternative pathway. This promoted NP recognition by human blood leukocytes and monocyte-derived macrophages. The macrophage capture of PMOXA-coated NPs correlates with sera donor variability in complement activation and opsonization but not with other major corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps

C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes

Poly­(2-methyl-2-oxazoline) (PMOXA) is an alternative promising polymer to poly­(ethylene glycol) (PEG) for design and engineering of macrophage-evading nanoparticles (NPs). Although PMOXA-engineered NPs have shown comparable pharmacokinetics and <i>in vivo</i> performance to PEGylated stealth NPs in the murine model, its interaction with elements of the human innate immune system has not been studied. From a translational angle, we studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived organically modified silica NPs (PMOXA-coated NPs) of approximately 100 nm in diameter with human complement system, blood leukocytes, and macrophages and compared their performance with PEGylated and uncoated NP counterparts. Through detailed immunological and proteomic profiling, we show that PMOXA-coated NPs extensively trigger complement activation in human sera exclusively through the classical pathway. Complement activation is initiated by the sensing molecule C1q, where C1q binds with high affinity (<i>K</i>_d = 11 ± 1 nM) to NP surfaces independent of immunoglobulin binding. C1q-mediated complement activation accelerates PMOXA opsonization with the third complement protein (C3) through the amplification loop of the alternative pathway. This promoted NP recognition by human blood leukocytes and monocyte-derived macrophages. The macrophage capture of PMOXA-coated NPs correlates with sera donor variability in complement activation and opsonization but not with other major corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps

C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes

Poly­(2-methyl-2-oxazoline) (PMOXA) is an alternative promising polymer to poly­(ethylene glycol) (PEG) for design and engineering of macrophage-evading nanoparticles (NPs). Although PMOXA-engineered NPs have shown comparable pharmacokinetics and <i>in vivo</i> performance to PEGylated stealth NPs in the murine model, its interaction with elements of the human innate immune system has not been studied. From a translational angle, we studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived organically modified silica NPs (PMOXA-coated NPs) of approximately 100 nm in diameter with human complement system, blood leukocytes, and macrophages and compared their performance with PEGylated and uncoated NP counterparts. Through detailed immunological and proteomic profiling, we show that PMOXA-coated NPs extensively trigger complement activation in human sera exclusively through the classical pathway. Complement activation is initiated by the sensing molecule C1q, where C1q binds with high affinity (<i>K</i>_d = 11 ± 1 nM) to NP surfaces independent of immunoglobulin binding. C1q-mediated complement activation accelerates PMOXA opsonization with the third complement protein (C3) through the amplification loop of the alternative pathway. This promoted NP recognition by human blood leukocytes and monocyte-derived macrophages. The macrophage capture of PMOXA-coated NPs correlates with sera donor variability in complement activation and opsonization but not with other major corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps