Healthy Ageing: A Decision-Support Algorithm for the Patient-Specific Assignment of ICT Devices and Services.

In response to rapid population ageing, digital technology represents the greatest resource in supporting the implementation of active and healthy ageing principles at clinical and service levels. However, digital information platforms that deliver coordinated health and social care services for older people to cover their needs comprehensively and adequately are still not widespread. The present work is part of a project that focuses on creating a new personalised healthcare and social assistance model to enhance older people's quality of life. This model aims to prevent acute events to favour the elderly staying healthy in their own home while reducing hospitalisations. In this context, the prompt identification of criticalities and vulnerabilities through ICT devices and services is crucial. According to the human-centred care vision, this paper proposes a decision-support algorithm for the automatic and patient-specific assignment of tailored sets of devices and local services based on adults' health and social needs. This decision-support tool, which uses a tree-like model, contains conditional control statements. Using sequences of binary divisions drives the assignation of products and services to each user. Based on many predictive factors of frailty, the algorithm aims to be efficient and time-effective. This goal is achieved by adequately combining specific features, thresholds, and constraints related to the ICT devices and patients' characteristics. The validation was carried out on 50 participants. To test the algorithm, its output was compared to clinicians' decisions during the multidimensional evaluation. The algorithm reported a high sensitivity (96% for fall monitoring and 93% for cardiac tracking) and a lower specificity (60% for fall monitoring and 27% for cardiac monitoring). Results highlight the preventive and protective behaviour of the algorithm.

Reusable Cavitand-Based Electrospun Membranes for the Removal of Polycyclic Aromatic Hydrocarbons from Water.

The removal of toxic and carcinogenic polycyclic aromatic hydrocarbons (PAHs) from water is one of the most intractable environmental problems nowadays, because of their resistance to remediation. This work introduces a highly efficient, regenerable membrane for the removal of PAHs from water, featuring excellent filter performance and pH-driven release, thanks to the integration of a cavitand receptor in electrospun polyacrylonitrile (PAN) fibers. The role of the cavitand receptor is to act as molecular gripper for the uptake/release of PAHs. To this purpose, the deep cavity cavitand BenzoQxCav is designed and synthetized and its molecular structure is elucidated via X-Ray diffraction. The removal efficiency of the new adsorbent material toward the 16 priority PAHs is demonstrated via GC-MS analyses at ng L-1 concentration. A removal efficiency in the 32%, to 99% range is obtained. The regeneration of the membrane is performed by exploiting the pH-driven conformational switching of the cavitand between the vase form, where the PAHs uptake takes place, to the kite one, where the PAHs release occurs. The absorbance and regeneration capability of the membrane are successfully tested in four uptake/release cycles and the morphological stability.

Selective and Reversible Solvent Uptake in Tetra-4-(4-pyridyl)phenylmethane-based Supramolecular Organic Frameworks.

The dynamic behavior of supramolecular organic frameworks (SOFs) based on the rigid tetra-4-(4-pyridyl)phenylmethane (TPPM) organic tecton has been elucidated through 3D electron diffraction, X-ray powder diffraction and differential scanning calorimetry (DSC) analysis. The SOF undergoes a reversible single-crystal-to-single-crystal transformation when exposed to vapours of selected organic solvents, moving from a closed structure with isolated small voids to an expanded structure with solvated channels along the b axis. The observed selectivity is dictated by the fitting of the guest in the expanded SOF, following the degree of packing coefficient. The effect of solvent uptake on TPPM solid-state fluorescence was investigated, evidencing a significant variation in the emission profile only in the presence of chloroform.

Design and Synthesis of Piperazine-Based Compounds Conjugated to Humanized Ferritin as Delivery System of siRNA in Cancer Cells.

Gene expression regulation by small interfering RNA (siRNA) holds promise in treating a wide range of diseases through selective gene silencing. However, successful clinical application of nucleic acid-based therapy requires novel delivery options. Herein, to achieve efficient delivery of negatively charged siRNA duplexes, the internal cavity of "humanized" chimeric Archaeal ferritin (HumAfFt) was specifically decorated with novel cationic piperazine-based compounds (PAs). By coupling these rigid-rod-like amines with thiol-reactive reagents, chemoselective conjugation was efficiently afforded on topologically selected cysteine residues properly located inside HumAfFt. The capability of PAs-HumAfFt to host and deliver siRNA molecules through human transferrin receptor (TfR1), overexpressed in many cancer cells, was explored. These systems allowed siRNA delivery into HeLa, HepG2, and MCF-7 cancer cells with improved silencing effect on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression with respect to traditional transfection methodologies and provided a promising TfR1-targeting system for multifunctional siRNA delivery to therapeutic applications.

Multidentate, V-Shaped Pyridine Building Blocks as Tectons for Crystal Engineering.

The formation of supramolecular structural units through self-assembly is a powerful method to design new architectures and materials endowed with specific properties. With the aim of adding a group of versatile tectons to the toolkit of crystal engineers, we have devised and synthesised four new V-shaped building blocks characterised by an aryl acetylene scaffold comprising three substituted pyridine rings connected by two triple bonds. The judicious choice of different substituents on the pyridine rings provides these tectons with distinctive steric, electrostatic and self-assembly properties, which influence their crystal structures and their ability to form co-crystals. Co-crystals of the tectons with tetraiododifluorobenzene were obtained both via traditional and mechanochemical crystallisation strategies, proving their potential use in crystal engineering. The energetic contributions of the supramolecular interactions at play in the crystal lattice have also been evaluated to better understand their nature and strength and to rationalise their role in designing molecular crystals.

Synthesis of Bromoundecyl Resorc[4]arenes and Applications of the Cone Stereoisomer as Selector for Liquid Chromatography.

As an extension of our studies on the multifaceted properties of C-alkylated resorc[4]arenes, we planned to immobilize on a solid support resorc[4]arenes with C11-long side chains in the lower rim. To this purpose, we synthesized two conformationally diverse resorc[4]arenes containing a bromoundecyl moiety in the four axial pendants. The cone stereoisomer 6a (30% yield) was selected for the reaction with an aminopropylated silica gel (APSG) obtained from spherical Kromasil Si 100, 5 µm particles, to give the corresponding immobilized SP-C11-resorc[4]arene system. The resulting polar-embedded stationary phase was fully characterized and investigated in the HPLC discrimination of the E/ Z stereoisomers of naturally occurring and semisynthetic combretastatins, a family of ( Z)-stilbene anticancer drugs. The chair stereoisomer 6b (20% yield), when submitted to X-ray diffraction analysis, showed a noteworthy self-assembly in the crystal lattice, with intercalated hydrophobic and polar layers as a result of intermolecular Br···O halogen bond interactions, according to a unique stacking motif. The potential and versatility of the SP-C11-resorc[4]arene stationary phase were shown as well in the separation of highly polar natural products (namely, flavonoids), under reversed-phase (RP) conditions, and of fullerenes C60 and C70, by using apolar solvents as mobile phases.

EPR interpretation, magnetism and biological study of a Cu(II) dinuclear complex assisted by a schiff base precursor.

A new Cu(II) dinuclear complex, Cu2L2 (1) was afforded employing the potentially pentatentate Schiff base precursor H2L, a refluxed product of o-vanillin and diethylenetriamine in methanol. Complex 1 was systematically characterized by FTIR, UV-Vis, emission and EPR spectrometry. The single crystal X-ray diffraction analysis of 1 reveals that the copper atom exhibits a distorted square planar geometry, comprising two pairs of phenolato-O and imine-N donors from two different H2L ligands. The temperature dependent magnetic interpretation agrees with the existence of weak antiferromagnetic interactions between the bridging dinuclear Cu(II) ions. A considerable body of experimental evidence has been accumulated to elucidate the magneto-structural relationship in this dinuclear Cu(II) complex by DFT computation. Both the ligand and complex 1 exhibit anti-mycobacterial activity and considerable efficacy on M. tuberculosis H37Ra (ATCC 25177) and M. tuberculosis H37Rv (ATCC 25618) strains. The practical applicability of the ligand and complex 1 has been examined in living cells (African Monkey Vero Cells). The MTT assay proves the non-toxicity of the probe up to 100 mg mL-1. A new homometallic dinuclear Cu(II) complex is afforded with a tetradentate Schiff base precursor. EPR interpretation and temperature dependent magnetic studies show that complex 1 has weak antiferromagnetic coupling and DFT computation is governed to explain the magneto-structural correlation.

Formation of Imidazo[1,5-a]pyridine Derivatives Due to the Action of Fe2+ on Dynamic Libraries of Imines.

An imidazo[1,5-a]pyridine derivative was unexpectedly obtained through the action of Fe2+ on a dynamic library of imines generated in situ via condensation of benzaldehyde and 2-picolylamine. The reaction product was easily isolated as the only nitrogen-containing product eluted from the chromatographic column. A reaction mechanism is proposed, in which combined kinetic and thermodynamic effects exerted by Fe2+ on the various steps of the complex reaction sequence are discussed. The Fe2+ nature of the added metal cation was found to be pivotal for the achievement of the imidazo[1,5-a]pyridine derivative as well as its amount in the reaction mixture. When the electronic effects were evaluated, gratifying yields were obtained only in the presence of moderately electron-releasing or moderately electron-withdrawing groups on the aldehyde reactant. No traces of imidazo[1,5-a]pyridine derivatives were obtained for p-OCH3 and p-NO2 benzaldehyde.

A Deep Insight into the Photoluminescence Properties of Schiff Base CdII and ZnII Complexes.

A tridentate N,N,O donor ligand 2,4-dichloro-2-[(2-piperazine-4-yl-ethylimino)-methyl]-phenol (HL) was designed, and eight new ZnII and CdII complexes, namely, [Zn(LH)(SCN)2] (1), [Zn(LH)(N3)2] (2), [Zn(LH)(NO2)2] (3), [Zn(LH)(dca)(OAc)] (4), [Cd2(LH)2(SCN)4] (5), [Cd(LH)(N3)2] (6), [Cd(LH)(NO2)2] (7), and [Cd(LH)(dca)(OAc)] (8) [where dca = dicyanamide anion] were synthesized. Five of them (1, 2, 4, 5, 7) were structurally characterized through single-crystal X-ray diffraction analysis. H-Bonding interactions are found to be the major stabilizing factor for crystallization in the solid state. Experimental and computational studies were performed in cooperation to provide a rationalization of the photoluminescence properties of those complexes. The quantum yields are anion-dependent, with enhanced efficiencies in the following order: LH < Cd-SCN(5) < Cd-dca(8) < Cd-N3(6) < Cd-NO2(7) < Zn-dca(4) < Zn-N3(2) < ZnNO2(3) < ZnSCN(1). By using quantum chemical calculations we rationalized the above trends. Moreover, the diverse lifetimes observed for those eight complexes were also quantitatively explained by considering the subtle competition between different photo-deactivation pathways.

Exclusive recognition of sarcosine in water and urine by a cavitand-functionalized silicon surface.

A supramolecular approach for the specific detection of sarcosine, recently linked to the occurrence of aggressive prostate cancer forms, has been developed. A hybrid active surface was prepared by the covalent anchoring on Si substrates of a tetraphosphonate cavitand as supramolecular receptor and it was proven able to recognize sarcosine from its nonmethylated precursor, glycine, in water and urine. The entire complexation process has been investigated in the solid state, in solution, and at the solid-liquid interface to determine and weight all the factors responsible of the observed specificity. The final outcome is a Si-based active surface capable of binding exclusively sarcosine. The complete selectivity of the cavitand-decorated surface under these stringent conditions represents a critical step forward in the use of these materials for the specific detection of sarcosine and related metabolites in biological fluids.

The effect of number and position of P=O/P=S bridging units on cavitand selectivity toward methyl ammonium salts.

The present work reports the synthesis and complexation properties of five mixed bridge P=O/P=S cavitands toward N,N-methyl butyl ammonium chloride (1) as prototype guest. The influence of number and position of P=O and P=S groups on the affinity of phosphonate cavitands toward 1 is assessed via ITC titrations in DCE as solvent. Comparison of the resulting Kass values, the enthalpic and entropic contributions to the overall binding with those of the parent tetraphosphonate Tiiii and tetrathiophosphonate TSiiii cavitands allows one to single out the simultaneous dual H-bond between the cavitand and the salt as the major player in complexation.

Cavitand-grafted silicon microcantilevers as a universal probe for illicit and designer drugs in water.

The direct, clean, and unbiased transduction of molecular recognition into a readable and reproducible response is the biggest challenge associated to the use of synthetic receptors in sensing. All possible solutions demand the mastering of molecular recognition at the solid-liquid interface as prerequisite. The socially relevant issue of screening amine-based illicit and designer drugs is addressed by nanomechanical recognition at the silicon-water interface. The methylamino moieties of different drugs are all first recognized by a single cavitand receptor through a synergistic set of weak interactions. The peculiar recognition ability of the cavitand is then transferred with high fidelity and robustness on silicon microcantilevers and harnessed to realize a nanomechanical device for label-free detection of these drugs in water.

Structural characterization of the supra-molecular complex between a tetra-quinoxaline-based cavitand and benzo-nitrile.

The structural characterization is reported of the supra-molecular complex between the tetra-quinoxaline-based cavitand 2,8,14,20-tetra-hexyl-6,10:12,16:18,22:24,4-O,O'-tetra-kis-(quinoxaline-2,3-di-yl)calix[4]resorcinarene (QxCav) with benzo-nitrile. The complex, of general formula C84H80N8O8·2C7H5N, crystallizes in the space group P with two independent mol-ecules in the asymmetric unit, displaying very similar geometrical parameters. For each complex, one of the benzo-nitrile mol-ecules is engulfed inside the cavity, while the other is located among the alkyl legs at the lower rim. The host and the guests mainly inter-act through weak C-H⋯π, C-H⋯N and dispersion inter-actions. These inter-actions help to consolidate the formation of supra-molecular chains running along the crystallographic b-axis direction.

Triptycene-based diiron(II) mesocates: spin-crossover in solution.

Triptycene-based diiron(II) and dizinc(II) mesocates were obtained using a novel rigid ligand with two pyridylbenzimidazole chelating units fused into the triptycene scaffold. Studies on the diiron(II) assembly in solution showed that the complex undergoes thermal-induced one-step spin-crossover with T1/2 at 243 K (Evans method).

Magnetic study and DFT analysis of a doubly carboxylato-bridged Co(II) derivative anchored with a 'scorpionate' precursor as a potential electrocatalyst for heterogeneous H2 evolution.

A new doubly carboxylato-bridged Co(II) dinuclear complex, [Co(bdtbpza)(NCS)]2 (1), was obtained in a satisfactory yield by employing a 'scorpionate'-type precursor, bdtbpza {bis-(3,5-di-tert-butylpyrazol-1-yl)acetate}, and was then structurally characterized. Single-crystal X-ray diffraction analysis revealed that, in 1, each Co(II) is penta-coordinated, leading to a distorted trigonal-bipyramidal geometry within the coordination environment of N3O2. Weak antiferromagnetic coupling within the Co(II) ions in 1 was found based on the isotropic spin Hamiltonian H = -J(S1·S2) for the Si = 3/2 system. For evaluating the spin density distribution and the mechanism for the magnetic exchange coupling, DFT analysis was performed, with the calculated result agreeing the experimental magnetic data. A study into electrochemical H2 evolution, involving cyclic voltammetry (CV), controlled potential electrolysis (CPE), and gas chromatographic (GC) analyses of the graphite electrode modified with the cobalt complex in a neutral aqueous solution revealed the high catalytic activity of the complex with a low overpotential toward H2O reduction. The faradaic efficiency of the catalyst was found to be 83.7% and the di-cobalt catalyst-modified electrode displayed quite an interesting H2-evolution activity compared with that of bare electrodes. These results are encouraging for the future potential application of 1 in water splitting.

Golden oldies: ten crystallography articles that we think must be read.

We have selected a set of ten 'golden oldies', diverse crystallography articles to illustrate important moments in the development of our field of science and which form landmark papers in crystallography. They are a mixture of 'science pull and technology push'. For each of our choices, we firstly created a new title that emphasizes how the paper's importance worked out from today's perspective. Then we describe the core details and impacts of each paper, with some quotations and a selected figure or two. Ten is an arbitrary number of highlights and our choice is personal.

Stimuli-Responsive, Dynamic Supramolecular Organic Frameworks.

Supramolecular organic frameworks (SOFs) are a class of three-dimensional, potentially porous materials obtained by the self-assembly of organic building blocks held together by weak interactions such as hydrogen bonds, halogen bonds, π⋅⋅⋅π stacking and dispersion forces. SOFs are being extensively studied for their potential applications in gas storage and separation, catalysis, guest encapsulation and sensing. The supramolecular forces that guide their self-assembly endow them with an attractive combination of crystallinity and flexibility, providing intelligent dynamic materials that can respond to external stimuli in a reversible way. The present review article will focus on SOFs showing dynamic behaviour when exposed to different stimuli, highlighting fundamental aspects such as the combination of tectons and supramolecular interactions involved in the framework formation, structure-property relationship and their potential applications.

3D electron diffraction analysis of a novel, mechanochemically synthesized supramolecular organic framework based on tetrakis-4-(4-pyridyl)phenylmethane.

Tetrakis-4-(4-pyridyl)phenylmethane (TPPM) is a tetrahedral rigid molecule that crystallizes forming a dynamically responsive supramolecular organic framework (SOF). When exposed to different stimuli, this supramolecular network can reversibly switch from an empty to a filled solvated solid phase. This article describes a novel expanded form of a TPPM-based SOF that has been mechanochemically synthesized and whose crystal structure has been determined by 3D electron diffraction analysis using a novel electron diffractometer.

Switching from separated to contact ion-pair binding modes with diastereomeric calix[4]pyrrole bis-phosphonate receptors.

We describe the design, synthesis and conformational assignment of three diasteromeric bis-phosphonate cavitands based on an aryl extended calix[4]pyrrole tetrol scaffold. The diastereoisomers differ in the relative spatial orientation of the P═O groups installed at their upper rims. We demonstrate that these compounds act as heteroditopic receptors for ion pairs forming ion-paired 1:1 complexes with alkylammonium (quaternary and primary) chloride salts in dichloromethane (DCM) solution and in the solid-state. (1)H NMR titrations indicate that the complexes are highly stable thermodynamically and kinetically. In the case of tetraalkyl-phosphonium/ammonium chloride guests, the host featuring the two P═O groups directed outwardly with respect to the aromatic cavity, 4oo, produces the most thermodynamically stable complexes. Conversely, for the primary alkyl ammonium chloride, the most effective receptor is the diastereoisomer 4ii with the two P═O groups converging on top of the aromatic cavity. In the nonpolar DCM solvent, the size of the quaternary cation has a strong impact in the thermodynamic stability of the complexes and their binding geometry. We use 2D-ROESY experiments to map out the binding geometries of the 1:1 complexes formed in solution. The 1:1 complexes of the 4oo host with the chloride salts have a separated arrangement of the bound ion-pair. In contrast, those of the 4ii host display a close-contact arrangement. We also investigate the same complexation processes in acetonitrile (ACN) solution. Both the salt and the initially formed anionic complex are fully dissociated in this more polar solvent. The receptors show an analogous trend in their binding affinities for quaternary phosphonium/ammonium chloride salts to the one seen in DCM solution. However, in ACN solution, the magnitudes of the binding affinities are reduced significantly and the size of the cation does not play a role. In addition, the inversion in the trend of relative binding affinities of the complexes, which was revealed in DCM solution, is eradicated in ACN when changing the cation substitution from quaternary to primary.

The four Rs and crystal structure analysis: reliability, reproducibility, replicability and reusability.

Within science, of which crystallography is a key part, there are questions posed to all fields that challenge the trust in results. The US National Academies of Sciences, Engineering and Medicine published a thorough report in 2019 on the Reproducibility and Replicability of Science: replicability being where a totally new study attempts to confirm if a phenomenon can be seen independently of another study. Data reuse is a key term in the FAIR data accord [Wilkinson et al. (2016). Sci. Data, 3, 160018], where the acronym FAIR means findable, accessible, interoperable and reusable. In the social sciences, the acronym FACT (namely fairness, accuracy, confidentiality and transparency) has emerged, the idea being that data should be FACTual to ensure trust [van der Aalst et al. (2017). Bus. Inf. Syst. Eng. 59, 311-313]. A distinction also must be made between accuracy and precision; indeed, the authors' lectures at the European Crystallography School ECS6 independently emphasized the need for use of other methods as well as crystal structure analysis to establish accuracy in biological and chemical/material functional contexts. The efforts by disparate science communities to introduce new terms to ensure trust have merit for discussion in crystallographic teaching commissions and possible adoption by crystallographers too.