196,196 research outputs found
The route towards nanoparticle shape metrology
No full textAn approach to identify and classify different shapes of nanomaterials starting from transmission electron microscopy images could be a powerful instrument to categorize the different shapes of nanoparticles and fingerprint the geometrical variability of an ensemble
Computational DFT Investigation of Vicinal Amide Group Anchimeric Assistance in Ether Cleavage
No full textThe devil and holy water: Protein and carbon nanotube hybrids
No full textIntegrating carbon nanotubes (CNTs) with biological systems to form hybrid functional assemblies is an innovative research area with great promise for medical, nanotechnology, and materials science applications. The specifics of molecular recognition and catalytic activity of proteins combined with the mechanical and electronic properties of CNTs provides opportunities for physicists, chemists, biologists, and materials scientists to understand and develop new nanomachines, sensors, or any of a number of other molecular assemblies. Researchers know relatively little about the structure, function, and spatial orientation of proteins noncovalently adsorbed on CNTs, yet because the interaction of CNTs with proteins depends strongly on the tridimensional structure of the proteins, many of these questions can be answered in simple terms. In this Account, we describe recent research investigating the properties of CNT/protein hybrids. Proteins act to solvate CNTs and may sort them according to diameter or chirality. In turn, CNTs can support and immobilize enzymes, creating functional materials. Additional applications include proteins that assemble ordered hierarchical objects containing CNTs, and CNTs that act as protein carriers for vaccines, for example. Protein/CNT hybrids can form bioscaffolds and can serve as therapeutic and imaging materials. Proteins can detect CNTs or coat them to make them biocompatible. One of the more challenging applications for protein/CNT hybrids is to make CNT substrates for cell growth and neural interfacing applications. The challenge arises from the structures' interactions with living cells, which poses questions surrounding the (nano)toxicology of CNTs and whether and how CNTs can detect biological processes or sense them as they occur. The surface chemistry of CNTs and proteins, including interactions such as π-π stacking interactions, hydrophobic interactions, surfactant-like interactions, and charge-π interactions, governs the wealth of structures, processes, and functions that appear when such different types of molecules interact. Each residue stars in one of two main roles, and understanding which residues are best suited for which type of interaction can lead to the design of new hybrids. Nonlocally, the peptide or protein primary, secondary, and tertiary structures govern the binding of proteins by CNTs. The conjugation of proteins with CNTs presents some serious difficulties both experimentally and culturally (such as bridging the "jargon barrier" across disciplines). The intersection of these fields lies between communities characterized by distinctly different approaches and methodologies. However, the examples of this Account illustrate that when this barrier is overcome, the exploitation of hybrid CNT-protein systems offers great potential
In Silico Carborane Docking to Proteins and Potential Drug Targets
No full textThe presence of boron atoms has made carboranes, C2B10H12, attractive candidates for boron neutron capture therapy. Because of their chemistry and possible conjugation with proteins, they can also be used to enhance interactions between pharmaceuticals and their targets and to increase the in vivo stability and bioavailability of compounds that are normally metabolized rapidly. Carboranes are isosteric to a rotating phenyl group, which they can substitute successfully in biologically active systems. A reverse ligand–protein docking approach was used in this work to identify binding proteins for carboranes. The screening was carried out on the drug target database PDTD that contains 1207 entries covering 841 known potential drug targets with structures taken from the Protein Data Bank. First, for validation, the protocol was applied to three crystal structures of proteins in which carborane derivatives are present. Then, the model was applied to systems for which the protein structure is available, but the binding site of carborane has not been reported. These systems were used for further validation of the protocol, while simultaneously providing new insight into the interactions between cage and protein. Finally, the screening was carried out on the database to reveal potential carborane binding targets of interest for biological and pharmacological activity. Carboranes are predicted to bind well to protease and metalloprotease enzymes. Other carborane pharmaceutical targets are also discussed, together with possible protein carriers
Fullerene sorting proteins
No full textProteins bind fullerenes. Hydrophobic pockets can accommodate a carbon cage either in full or in part. However, the identification of proteins able to discriminate between different cages is an open issue. Prediction of candidates able to perform this function is desirable and is achieved with an inverse docking procedure that accurately accounts for (i) van der Waals interactions between the cage and the protein surface, (ii) desolvation free energy, (iii) shape complementarity, and (iv) minimization of the number of steric clashes through conformational variations. A set of more than 1000 protein structures is divided into four categories that either select C(60) or C(70) (p-C(60) or p-C(70)) and either accommodate the cages in the same pocket (homosaccic proteins, from σακκoζ meaning pocket) or in different pockets (heterosaccic proteins). In agreement with the experiments, the KcsA Potassium Channel is predicted to have one of the best performances for both cages. Possible ways to exploit the results and efficiently separate the two cages with proteins are also discussed
Incorporation of Molecular Nanoparticles Inside Proteins: The Trojan Horse Approach in Theranostics
No full textCONSPECTUS: Molecular nanoparticles, MNPs, characterized by well-defined chemical formulas, structures, and sizes can interact with a variety of proteins. Fullerenes, carboranes, and gold nanoclusters well represent the diversity of MNPs properties available in nanoscience. They can have diameters smaller than 1.5 nm, be hydrophilic or hydrophobic, and can use a paraphernalia of means to establish local and global interactions with the amino acidic residues of proteins. Proteins, endowed as they are with an assortment of pockets, crevices, and gaps are natural supramolecular hosts to incorporate/hide/transport MNPs directly in water with a facile and "green" approach.This Account identifies and discusses the rules that govern the interactions and binding between MNPs and proteins. Fullerenes are composed solely by carbon atoms arranged to form hollow polyhedra. Hydrophobic interactions occur between aliphatic residues and the fullerene surface. The amino acids most effectively interacting with fullerenes are aromatic residues that establish p-p stacking interactions with the cage. Amphiphilic and charged residues produce also cation-p, anion-p, and surfactant-like interactions with the cages.Carboranes are composed of boron, carbon, and hydrogen atoms, also arranged to form cages. They are hydrophobic with unusual properties originating from the presence of boron atoms. Hydride-like hydrogens bound to the boron atoms govern carborane chemistry. These negatively charged hydrogens do not participate in classic hydrogen bonding with water and promote hydrophobic interactions with proteins. On the contrary, the electronegativity of these hydrogens drives the formation of unconventional dihydrogen bonds with the acidic hydrogen atoms of positively charged amino acid. Carboranes also establish C-H center dot center dot center dot p and B-H center dot center dot center dot p interactions with aromatic residues.Gold nanoclusters, AuNCs, are synthesizable with atomically precise stoichiometry. Amino acid residues with sulfur atoms or with nitrogen-containing heterocycles are the strongest Au binders. The proteins can act as supramolecular hosts but also as templates for the synthesis of AuNCs directly inside the protein core. Of the pristine amino acids, tryptophan, tyrosine, phenylalanine, and aspartic acid are the most efficient reducing groups. In a peptide sequence, the best Au-reducing moieties are obtained by nitrogencontaining residue such as glutamine, asparagine, arginine, and lysine. The investigation of the interactions between AuNCs and proteins therefore adds further complexity with respect to that of fullerenes and carboranes. The selection of the host proteins should consider that they will have to contain active sites for metal ion accumulation and ion reduction where AuNC can form and stabilize. This Account further discusses the hybridization of MNPs with proteins in view of creating innovative multifunctional theranostic platforms where the role of proteins is akin to that of "Trojan Horses" since they can (i) hide the MNPs, (ii) control their cellular uptake, (iii) drive their crossing of physiological barriers, and (iv) ultimately govern their biological fate
Development of an innovative method for real-time monitoring and control of comfort in indoor environments based on dynamic measurements of personal parameters
No full textIl benessere degli occupanti è uno degli aspetti fondamentali da considerare nella progettazione e gestione degli edifici. Le condizioni del microclima hanno un impatto significativo sia sulla salute che sulla produttività.
Considerando il modello di Fanger, il comfort termico è un aspetto complesso poiché dipende sia da parametri ambientali che personali (tasso metabolico (M) e isolamento termico del vestiario (Icl)). I primi sono facilmente misurabili con reti di sensori, mentre fornire una stima corretta delle variabili fisiologiche è molto complesso data la necessità di acquisire parametri sulla persona. Nel presente lavoro di tesi sono state sviluppate nuove metodologie per la misura real-time dei parametri personali per migliorare la valutazione del comfort termico.
Per quanto riguarda M, è stata sviluppata una metodologia che si basa su misurazioni continue della frequenza cardiaca e di altri parametri fisiologici adottando un dispositivo indossabile per acquisire i dati. I test effettuati in laboratorio hanno permesso di ricavare una relazione che fornisce una misura dinamica del tasso metabolico. La valutazione dinamica dell’isolamento termico dovuto al vestiario è effettuata su base giornaliera ed è ricavata in funzione delle condizioni climatiche esterne. Inoltre, è stato sviluppato un banco di prova virtuale per testare l'impatto del sistema sulla gestione degli edifici. È stato utilizzato un modello di simulazione di un edificio per testare un controllo della temperatura dell'aria basato su PMV. Infine, è stata effettuata l'analisi d'incertezza allo scopo di studiare l'impatto dei metodi sviluppati. I risultati mostrano un miglioramento nella gestione del comfort. Le metodologie sviluppate sono state adottate in un caso studio reale in cui la valutazione del comfort termico è stata eseguita utilizzando un sistema innovativo (Comfort Eye). Esso permette il monitoraggio in tempo reale del comfort termico. Inoltre, il sistema di monitoraggio del comfort è stato integrato con un sistema di building management.The well-being of buildings’ occupants is one of the main aspects to be considered in buildings design and management. The indoor environment significantly impacts both health and productivity. The present work aims to provide a deep investigation of comfort aspects, focusing on thermal comfort.
Thermal comfort is a complex aspect since it depends on both environmental and physiological quantities. Considering the Fangers’ model, the environmental parameters can be easily monitored with sensors networks, whereas to provide a good evaluation of the physiological variables is more difficult. The personal parameters greatly affect the evaluation of the indoor thermal comfort. Therefore, this work presents new methodologies for both the real-time and dynamic estimation of those parameters to improve thermal comfort assessment.
Regarding the metabolic rate parameter, the methodology is based on the heart rate measurements coupled with other physiological parameters. Thus, a wearable multi-parametric device was adopted to collect data and tests were conducted to find the best relationship for the estimation of metabolic rate. Conversely, the dynamic evaluation of clothing insulation was derived from the external climate conditions. A virtual test bench was developed to test the impact of the system on building management. A simulation model of a building was used to test a PMV-based air temperature controller. The uncertainty analysis was conducted to study the impact of the proposed methods. The results showed an improvement of comfort management. The methodologies were adopted in a real case study in which the evaluation of indoor thermal comfort was performed by using an innovative system (the Comfort Eye). It allows the real-time monitoring of indoor thermal comfort based on the Fangers’ model. To reach this scope a new version of the Comfort Eye system was developed and it was integrated with a building management system
In Vivo Application of Carboranes for Boron Neutron Capture Therapy (BNCT): Structure, Formulation and Analytical Methods for Detection
No full textCarboranes have emerged as one of the most promising boron agents in boron neutron capture therapy (BNCT). In this context, in vivo studies are particularly relevant, since they provide qualitative and quantitative information about the biodistribution of these molecules, which is of the utmost importance to determine the efficacy of BNCT, defining their localization and (bio)accumulation, as well as their pharmacokinetics and pharmacodynamics. First, we gathered a detailed list of the carboranes used for in vivo studies, considering the synthesis of carborane derivatives or the use of delivery system such as liposomes, micelles and nanoparticles. Then, the formulation employed and the cancer model used in each of these studies were identified. Finally, we examined the analytical aspects concerning carborane detection, identifying the main methodologies applied in the literature for ex vivo and in vivo analysis. The present work aims to identify the current strengths and weakness of the use of carboranes in BNCT, establishing the bottlenecks and the best strategies for future applications
A Mechanistic Insight into the Cu(II)-Catalyzed C–N and C–O Coupling Reaction of Arylglyoxylic Acids with Isatins; A DFT Investigation
No full textWe carried out a DFT computational investigation on the mechanism of the copper(II) catalyzed C–N, C–O cross coupling reaction involving isatin and phenylglyoxylic acid recently reported by Gogoi. The mechanistic hypothesis proposed by this author is overall confirmed. Our computations demonstrated that the initial decarboxylation is an exergonic reaction (–15.3 kcal mol–1). This process, which can occur rather easily under the used experimental conditions (95 °C for 24 hours), triggers the catalytic cycle with the formation of the initial active organometallic complex (I1). A copper acetate ligand deprotonates the isatin nitrogen. This enhances its nucleophilic character and makes possible the attack of nitrogen on the Cu atom. A reversible transformation connects the initial encounter complex between isatin and the active intermediate I1 and the intermediate where the metal atom inserts into the amide bond. The decarbonylation step represents the rate-determining step of the entire process (activation free energy = 23.3 kcal mol–1). Copper does not change its oxidation state (II) in the course of the catalytic reaction. The mechanism never involves directly the isatin benzene ring: this is consistent with the fact that only slight changes in the reaction yield are observed when substituents are inserted at different positions of the aromatic ring
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