Hybrid nanoreceptors for high sensitivity detection of small molecules by NMR chemosensing

Self-assembled gold nanoparticles onto colloidal silica nanoparticles exhibited higher magnetization transfer efficiencies in NMR chemosensing experiments, allowing the detection of analytes as low as 10 μM

Nanoparticle-based receptors mimic protein-ligand recognition

The self-assembly of a monolayer of ligands on the surface of noble metal nanoparticles dictates the fundamental nanoparticle\u2019s behavior and its functionality. In this combined computational\u2013experimental study, we analyze the structure, organization, and dynamics of functionalized coating thiols in monolayer-protected gold nanoparticles (AuNPs). We explain how functionalized coating thiols self-organize through a delicate and somehow counterintuitive balance of interactions within the monolayer itself and with the solvent. We further describe how the nature and plasticity of these interactions modulate nanoparticle-based chemosensing. Importantly, we found that self-organization of coating thiols can induce the formation of binding pockets in AuNPs. These transient cavities can accommodate small molecules, mimicking protein-ligand recognition, which may explain the selectivity and sensitivity observed for different organic analytes in NMR chemosensing experiments. Thus, our findings advocate for the rational design of tailored coating groups to form specific recognition binding sites on monolayer-protected AuNPs

Optically Enhanced Solid-State ¹H NMR Spectroscopy

International audienceLow sensitivity is the primary limitation toextending nuclear magnetic resonance (NMR) techniques tomore advanced chemical and structural studies. Photochemicallyinduced dynamic nuclear polarization (photo-CIDNP) is an NMRhyperpolarization technique where light is used to excite a suitabledonor−acceptor system, creating a spin-correlated radical pairwhose evolution drives nuclear hyperpolarization. Systems thatexhibit photo-CIDNP in solids are not common, and this effecthas, up to now, only been observed for 13C and 15N nuclei.However, the low gyromagnetic ratio and natural abundance ofthese nuclei trap the local hyperpolarization in the vicinity of thechromophore and limit the utility for bulk hyperpolarization. Here,we report the first example of optically enhanced solid-state 1HNMR spectroscopy in the high-field regime. This is achieved viaphoto-CIDNP of a donor−chromophore−acceptor molecule in a frozen solution at 0.3 T and 85 K, where spontaneous spindiffusion among the abundant strongly coupled 1H nuclei relays polarization through the whole sample, yielding a 16-fold bulk 1Hsignal enhancement under continuous laser irradiation at 450 nm. These findings enable a new strategy for hyperpolarized NMRbeyond the current limits of conventional microwave-driven DNP

Excellent outcomes of 2G-TKI therapy after imatinib failure in chronic phase CML patients

Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib and nilotinib produced historical rates of about 50% complete cytogenetic response (CCyR) and about 40% major molecular response (MMR) in chronic myeloid leukaemia (CML) patients failing imatinib. Direct comparisons between dasatinib and nilotinib are lacking, and few studies addressed the dynamics of deep molecular response (DMR) in a "real-life" setting. We retrospectively analyzed 163 patients receiving dasatinib (n= 95) or nilotinib (n= 68) as second-line therapy after imatinib. The two cohorts were comparable for disease's characteristics, although there was a higher rate of dasatinib use in imatinib-resistant and of nilotinib in intolerant patients. Overall, 75% patients not in CCyR and 60% patients not in MMR at 2G-TKI start attained this response. DMR was achieved by 61 patients (37.4%), with estimated rate of stable DMR at 5 years of 24%. After a median follow-up of 48 months, 60% of patients persisted on their second-line treatment. Rates and kinetics of cytogenetic and molecular responses, progression-free and overall survival were similar for dasatinib and nilotinib. In a "real-life" setting, dasatinib and nilotinib resulted equally effective and safe after imatinib failure, determining high rates of CCyR and MMR, and a significant chance of stable DMR, a prerequisite for treatment discontinuation

Matrix-Assisted NMR

During the last decades, the interest of chemistry toward increasingly sophisticated processes has grown exponentially. As a consequence, the evolution of the systems under investigation has been necessarily paired with the development of modern methodologies capable of handling the enormous amount of data stemming from samples of great complexity. Among the many examples in the literature, one of the biggest ongoing challenges is the analysis of mixtures, from reaction crude extracts to biological fluids like blood and urine. Indeed, chromatography has been - and still remains - one of the primary methods adopted to reduce the complexity of a multi-analyte system. Nonetheless, one intrinsic problem of the chromatographic approach is its inability to identify unknown molecules, and hyphenated techniques (mostly based on mass spectroscopy) have been developed just to overcome this stumbling block. On the other hand, Nuclear Magnetic Resonance (NMR) spectroscopy is one of the most powerful techniques for the investigation of organic compounds. NMR exploits an intrinsic property exhibited by some atomic nuclei -- the spin -- to acquire chemical and structural information through well-established experimental protocols, known as pulse sequences. In particular, solution-state NMR can boast a vast ensemble of procedures aimed at collecting detailed data about through bond connectivities (COSY, TOCSY, HSQC,...) or through space proximities (NOESY, ROESY,...). All these information are nothing less than fundamental for the structure determination of unknown compounds. Even tough this makes NMR spectroscopy largely appealing, the acquisition of such extensive information ultimately translates into detecting many signals at once, so that spectra interpretation can become a very challenging task. This is especially true when observing 1H resonances, which display a small dispersion in the frequency domain (about 12 ppm) and spectral crowding becomes consequently a serious problem. Not surprisingly, the situation becomes almost unmanageable when NMR is applied to the assay of mixtures, where the superposition of signals stemming from different species is virtually assured. Certainly, multidimensional NMR techniques can be useful for the interpretation of crowded single-molecule spectra, but they rapidly loose all their advantages as the number of components in the sample increases. As for chromatography, the advent of hybrid techniques like LC-NMR, where LC stands for Liquid Chromatography, has partly circumvented the aforementioned difficulties, yet at the cost of an expensive and dedicated instrumentation. In the context of mixture analysis, matrix-assisted NMR methodologies stand as an alternative to the various hyphenated techniques. They rely on the combination of NMR spectroscopy and an external agent added to the sample, which can be either a molecular or macromolecular species, or even a mesoscopic matrix. The aim of such matrices is to differentiate the signals of the various components, favouring their detection and characterisation. The present work is divided into three independent parts. The first two are dedicated to different subjects of matrix-assisted NMR. In particular, Part I is aimed at the understanding of the physical phenomena underlying signal broadening when a solid, stationary phase is used in Matrix-Assisted Diffusometry (MAD) NMR measurements. Part II focuses on nanoparticle-assisted NMR chemosensing, a technique where monolayer-protected gold nanoparticles are exploited to transfer magnetization to selected classes of analytes by means of the Nuclear Overhauser Effect. In this second part, different nanoparticle-assisted methodologies are presented and analysed, alongside with some strategies aimed at the enhancement of the sensitivity. Part III concerns the complete 1H-NMR characterisation of the atomically precise Au38(SBut)24 gold nanocluster, which can be considered as a prototypical nanoparticle. The Au38 core features four different symmetry-unique and equally populated binding sites for the grafting of the ligands that constitute the coating monolayer. Each binding site shows a distinct pattern of resonances, so that the overall 1H-NMR spectrum of the cluster is the result of the superposition of four independent subspectra. In this case, the full characterisation of the spectrum has been achieved through a combined NMR-MD (Molecular Dynamics) analysis

Chromatographic NMR spectroscopy: the effect of hollow silica microspheres on magnetic field inhomogeneities and resonance lineshapes

Micrometric hollow silica spheres can effectively reduce magnetic field inhomogeneities when employed as a stationary phase in the context of NMR chromatography. We here provide a description of the NMR line broadening phenomenon for physically representative collections of hollow spheres with different geometries and filling factors. Our results highlight how, within the explored conditions, a proper modelling of the line broadening phenomenon should consider the enhanced relaxation of the spins during their diffusion across the spherical shells, and possibly other slow motional effects

ITSs for Transnational Road Traffic Detection: An Opportunity for More Reliable Data

Reliable data collection is an unavoidable requisite for rigorous planning of transport policies that aim at achieving a more balanced modal split. This is particularly evident for long-distance road traffic, which in most cases involves two or more countries. Since each country adopts its own method for counting and classifying vehicles, the risk of using inconsistent data for common purposes is high. Intelligent Transport Systems may be a valid support for providing a standardized and effective method to solve this issue, provided that there is a preliminary agreement on the technological solutions and the location where to install them. This paper compares the methods currently adopted by different stakeholders and authorities in Italy and Austria to count transnational heavy and light vehicles along the Brenner corridor, which is one of the main European transnational axes in terms of traffic volumes. In line with this analysis, differences in the results could be noted, according to the adopted method and their position. Subsequently, a solution to achieve a more consistent dataset is proposed, based on common classification and shared technology to detect vehicles. This agreement is fundamental for policy purposes: the main aim of the Italian-Austrian Euregio Tyrol-South Tyrol-Trentino in the transport sector is to invert the current long-distance modal split by 2035, a result that can be achieved only if a correct and shared counting system is adopted. © 2021, Springer Nature Switzerland AG

ITSs for Transnational Road Traffic Detection: An Opportunity for More Reliable Data

Reliable data collection is an unavoidable requisite for rigorous planning of transport policies that aim at achieving a more balanced modal split. This is particularly evident for long-distance road traffic, which in most cases involves two or more countries. Since each country adopts its own method for counting and classifying vehicles, the risk of using inconsistent data for common purposes is high. Intelligent Transport Systems may be a valid support for providing a standardized and effective method to solve this issue, provided that there is a preliminary agreement on the technological solutions and the location where to install them. This paper compares the methods currently adopted by different stakeholders and authorities in Italy and Austria to count transnational heavy and light vehicles along the Brenner corridor, which is one of the main European transnational axes in terms of traffic volumes. In line with this analysis, differences in the results could be noted, according to the adopted method and their position. Subsequently, a solution to achieve a more consistent dataset is proposed, based on common classification and shared technology to detect vehicles. This agreement is fundamental for policy purposes: the main aim of the Italian-Austrian Euregio Tyrol-South Tyrol-Trentino in the transport sector is to invert the current long-distance modal split by 2035, a result that can be achieved only if a correct and shared counting system is adopted. © 2021, Springer Nature Switzerland AG

Uniform water-mediated saturation transfer: a sensitivity-improved alternative to WaterLOGSY

In the study of small molecule ligands and candidate macromolecular targets, water spins in long-lived association with macromolecules (proteins or nanoparticles) constitute a remarkable source of magnetization that can be exploited to reveal ligand-target binding. In this work we show how the selective saturation of water spins complemented with adiabatic off-resonance spin-locks can remove the NOE contribution of bulk water in the final difference spectrum, leading to uniformly enhanced signals that reveal weak ligand-target interactions