Insight into Protein–Polymer Conjugate Relaxation Dynamics: The Importance of Polymer Grafting

The bio and chemical physics of protein–polymer conjugates are related to parameters that characterize each component. With this work, it is intended to feature the dynamical properties of the protein–polymer conjugate myoglobin (Mb)–poly(ethyl ethylene phosphate), in the ps and ns time scales, in order to understand the respective roles of the protein and of the polymer size in the dynamics of the conjugate. Elastic and quasi‐elastic neutron scattering is performed on completely hydrogenated samples with variable number of polymer chains covalently attached to the protein. The role of the polymer length in the protein solvation and internal dynamics is investigated using two conjugates formed by polymers of different molecular weight. It is confirmed that the flexibility of the complex increases with the number of grafted polymer chains and that a sharp dynamical transition appears when either grafting density or polymer molecular weight are high. It is shown that protein size is crucial for the polymer structural organization and interaction on the protein surface and it is established that the glass properties of the polymer change upon conjugation. The results give a better insight of the equivalence of the polymer coating and the role of water on the surface of proteins.     

Mechanically-Driven Vase–Kite Conformational Switch in Cavitand Cross-Linked Polyurethanes

The eligibility of tetraquinoxaline cavitands (QxCav) as molecular grippers relies on their unique conformational mobility between a closed (vase) and an open (kite) form, triggered in solution by conventional stimuli like pH, temperature and ion concentration. In the present paper, the mechanochemical conformational switching of ad hoc functionalized QxCav covalently embedded in an elastomeric polydimethylsiloxane and in a more rigid polyurethane matrix is investigated. The rigid polymer matrix is more effective in converting mechanical force into a conformational switch at the molecular level, provided that all four quinoxaline wings are covalently connected to the polymer.     

Probenecid and benzamide: cocrystal prepared by a green method and its physico-chemical and pharmaceutical characterization

Journal of Thermal Analysis and Calorimetry - The eco-friendly method of kneading was here used to synthesize a cocrystal of probenecid, an uricosuric drug used in treating gout and hyperuricemia,...     

Parameters for Irreversible Inactivation of Monoamine Oxidase

The irreversible inhibitors of monoamine oxidases (MAO) slow neurotransmitter metabolism in depression and neurodegenerative diseases. After oxidation by MAO, hydrazines, cyclopropylamines and propargylamines form a covalent adduct with the flavin cofactor. To assist the design of new compounds to combat neurodegeneration, we have updated the kinetic parameters defining the interaction of these established drugs with human MAO-A and MAO-B and analyzed the required features. The K_i values for binding to MAO-A and molecular models show that selectivity is determined by the initial reversible binding. Common to all the irreversible inhibitor classes, the non-covalent 3D-chemical interactions depend on a H-bond donor and hydrophobic-aromatic features within 5.7 angstroms apart and an ionizable amine. Increasing hydrophobic interactions with the aromatic cage through aryl halogenation is important for stabilizing ligands in the binding site for transformation. Good and poor inactivators were investigated using visible spectroscopy and molecular dynamics. The initial binding, close and correctly oriented to the FAD, is important for the oxidation, specifically at the carbon adjacent to the propargyl group. The molecular dynamics study also provides evidence that retention of the allenyl imine product oriented towards FADH⁻ influences the formation of the covalent adduct essential for effective inactivation of MAO.     

Continuous‐Flow Synthesis of ZIF‐8 Biocomposites with Tunable Particle Size

Zeolitic imidazolate framework (ZIF) biocomposites show the capacity to protect and deliver biotherapeutics. To date, the progress in this research area is based on laboratory batch methods. Now, the first continuous flow synthetic method is presented for the encapsulation of a model protein (bovine serum albumin, BSA) and a clinical therapeutic (α1‐antitrypsin, AAT) in ZIF‐8. The in situ kinetics of nucleation, growth, and crystallization of BSA@ZIF‐8 were studied by small‐angle X‐ray scattering. By controlling the injection time of ethanol, the particle growth could be quenched by ethanol‐induced crystallization from amorphous particles to ZIF‐8 crystals. The particle size of the biocomposite was tuned in the 40–100 nm range by varying residence time prior to introduction of ethanol. As a proof‐of‐concept, this procedure was used for the encapsulation of AAT in ZIF‐8. Upon release of the biotherapeutic from the composite, the trypsin inhibitor function of AAT was preserved.     

Carbohydrate-Based Peptido Mimetics. Synthesis of Two New Scaffolds for Combinatorial Libraries.

The recent utilisation of the glucopyranose ring as scaffold for the synthesis of a potent somatostatin agonist demonstrated the use of monosaccharides as viable templates in drug design.^2,3 Monosaccharide-based mimics provide enantiomerically pure, rigid moieties (able to give precise orientation of functional groups), with a high degree of oxygenation to assure water solubility.⁴ Moreover, carbohydrates exhibit a high combinatorial density. These advantages prompted us to synthesise new monosaccharide derivatives as carbohydrate scaffolds for potential drug design.     

Tuning the Dipolar Second‐Order Nonlinear Optical Properties of Cyclometalated Platinum(II) Complexes with Tridentate N^C^N Binding Ligands

Appropriate functionalization of the cyclometalated ligand, L , and the choice of the ancillary ligand, X, allows the dipolar second‐order nonlinear optical response of luminescent [Pt L X] complexes—in which L is an N^C^N‐coordinated 1,3‐di(2‐pyridyl)benzene ligand and X is a monodentate halide or acetylide ligand—to be controlled. The complementary use of electric‐field‐induced second‐harmonic (EFISH) generation and harmonic light scattering (HLS) measurements demonstrates how the quadratic hyperpolarizability of this appealing family of multifunctional chromophores, characterized by a good transparency throughout much of the visible region, is dominated by an octupolar contribution.     

Computational Design,Synthesis, and Mechanochromic Properties of New Thiophene‐Based π‐Conjugated Chromophores

The possibility of exploiting supramolecular architectures for the preparation of innovative mechanochromic devices has been extended by designing novel thienyl‐substituted 1,4‐bis(ethynyl)benzene dyes, which are characterized by a conjugated, rigid, rodlike core structure. This new family of chromophores was synthesized according to a simple two‐step sequential cross‐coupling reaction, and the optical properties were investigated in solution and in a polymeric matrix. To tune the mechanochromic performances in smart polymer materials, a virtual screening was set up that was able to select a derivative with optimal spectral features. The effective combination of experimental and computational investigations allowed us to spot those homologues with already potential anisotropic and aggregachromic features and characterized by the best spectral properties and luminescent response. The best candidate was synthesized and dispersed into a polyethylene matrix, indeed achieving an “in silico designed” mechanochromic material. Besides the specific applications of this novel material, the integration of computational and experimental techniques reported here defines an efficient protocol that can be applied to make a selection among similar dye candidates, which constitute the essential responsive part of such supramolecular devices.     

Interfacial slip on rough,patterned and soft surfaces: A review of experiments and simulations

Advancements in the fabrication of microfluidic and nanofluidic devices and the study of liquids in confined geometries rely on understanding the boundary conditions for the flow of liquids at solid surfaces. Over the past ten years, a large number of research groups have turned to investigating flow boundary conditions, and the occurrence of interfacial slip has become increasingly well-accepted and understood. While the dependence of slip on surface wettability is fairly well understood, the effect of other surface modifications that affect surface roughness, structure and compliance, on interfacial slip is still under intense investigation. In this paper we review investigations published in the past ten years on boundary conditions for flow on complex surfaces, by which we mean rough and structured surfaces, surfaces decorated with chemical patterns, grafted with polymer layers, with adsorbed nanobubbles, and superhydrophobic surfaces. The review is divided in two interconnected parts, the first dedicated to physical experiments and the second to computational experiments on interfacial slip of simple (Newtonian) liquids on these complex surfaces. Our work is intended as an entry-level review for researchers moving into the field of interfacial slip, and as an indication of outstanding problems that need to be addressed for the field to reach full maturity.