Discovery and preliminary SAR of 5-arylidene-2,2-dimethyl-1,3-dioxane- 4,6-diones as platelet aggregation inhibitors

We herein document the discovery of 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6-diones as a novel family of platelet aggregation inhibitors. The preliminary optimization study enabled us to establish the most salient features of the structure-activity relationships in this series as well as to identify novel derivatives that are upto 60 times more potent than the hit structure 1 and slightly superior to the reference drug Milrinone.     

Intramolecular benzyl protection delivery: a practical synthesis of DMDP and DGDP from D-fructose

[reaction: see text] A two-step protection of 1,2-diols as the corresponding o-xylylene cyclic ethers, involving an intramolecular ring-closing O-benzylation reaction, has been developed to overcome the problems associated to regioselective benzylation reactions. The strategy has been applied to the high-yielding synthesis of the pyrrolidine glycosidase inhibitors DMDP and DGDP.     

Development of an in vitro confinement test to predict the clinical handling of polymer-based injectable bone substitutes

The objective of the current study was to present a simple and standardized system as a preliminary attempt to assess the confinement of polymer-based injectable bone substitutes (IBSs) in vitro. Four different types of polymer-based IBSs were selected as model compounds, a thermosensitive collagen gel, a colloidal gelatin gel, a covalently crosslinked oligo(poly(ethylene glycol)fumarate (OPF) gel and a OPF-calcium phosphate composite. A ceramic-based IBS (i.e. a self-setting calcium phosphate cement) was used as reference. The confinement of all IBSs was tested under three different conditions: (1) no flow (as control), (2) dynamic flow after injection and (3) dynamic flow during injection. The results presented herein confirmed that the proposed test can be used to quantify the confinement of various IBSs within artificial defects under static or dynamic flow conditions, thereby offering a potential tool for predictive quantitative determination of the confinement of IBSs in vivo.     

Ring-Opening Metathesis Polymerization Kinetics of Cyclooctene with Second Generation Grubbs’ Catalyst

A kinetic study of the ring-opening metathesis polymerization (ROMP) of cis-cyclooctene using the ruthenium initiator benzylidene [1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene]-dichloro-(tricyclohexylphosphine) (second generation Grubbs’ catalyst) was carried out by ¹H-NMR. The dependence on the reaction rate with the temperature and the influence of the addition of a chain transfer agent were evaluated. Some kinetic constants are also reported for this system.     

Error-Correcting Codes and Phase Transitions

The theory of error-correcting codes is concerned with constructing codes that optimize simultaneously transmission rate and relative minimum distance. These conflicting requirements determine an asymptotic bound, which is a continuous curve in the space of parameters. The main goal of this paper is to relate the asymptotic bound to phase diagrams of quantum statistical mechanical systems. We first identify the code parameters with Hausdorff and von Neumann dimensions, by considering fractals consisting of infinite sequences of code words. We then construct operator algebras associated to individual codes. These are Toeplitz algebras with a time evolution for which the KMS state at critical temperature gives the Hausdorff measure on the corresponding fractal. We extend this construction to algebras associated to limit points of codes, with non-uniform multi-fractal measures, and to tensor products over varying parameters.     

Structural and photophysical studies on a linear trinuclear zinc complex of 2-[(2-hydroxyethylimino)methyl]quinolin-8-ol

A linear trinuclear zinc complex was obtained when after refluxing 8-hydroxyquinoline-2-carboxaldehyde and 2-aminoethanol (in a 1:1 molar ratio) until the formation of the H₂L ligand, a methanol solution of zinc acetate dihydrate was added. Reaction between Zn(OAc)₂·2H₂O and H₂L, both in 3:2 or 4:2 ratios, yielded Zn₃(HL)₂(OAc)₄. This latter could be crystallographically characterised, and rather surprisingly, the potentially tetradentate HL⁻ is only acting as an O,N-donor, while two phenolate and four acetate bridges hold together the three zinc ions. A study of the luminescence properties in methanol solution showed that the quantum yield of Zn₃(HL)₂(OAc)₄ (Φ_F = 0.07) is slightly higher than that of 8-hydroxyquinoline-2-carboxaldehyde (Φ_F = 0.06).     

Applying the Retro‐Enantio Approach To Obtain a Peptide Capable of Overcoming the Blood–Brain Barrier

The blood–brain barrier (BBB) is a formidable physical and enzymatic barrier that tightly controls the passage of molecules from the blood to the brain. In fact, less than 2 % of all potential neurotherapeutics are able to cross it. Here, by applying the retro‐enantio approach to a peptide that targets the transferrin receptor, a full protease‐resistant peptide with the capacity to act as a BBB shuttle was obtained and thus enabled the transport of a variety of cargos into the central nervous system.     

Crystallisation Solvent Influence on the Crystal Structures of MnII and NiII Complexes with 2,6‐bis(1‐salicyloylhydrazonoethyl)pyridine,H4daps

Neutral manganese and nickel complexes of the empirical formulae Mn(H₂daps)(H₂O)_0.5 and Ni(H₂daps) · (H₂O)_1.5(CH₃CN) have been prepared by electrochemical syntheses. The structures of the complexes formed from solvents with different donor ability were investigated. Recrystallisation of Mn(H₂daps)(H₂O)_0.5 from pyridine and ethanol yields [Mn(H₂daps)(py)₂] 1 and [Mn(H₂daps)(C₂H₅OH) · (H₂O)] 2 . Slow evaporation of dichloromethane and methanol solutions of Ni(H₂daps)(H₂O)_1.5(CH₃CN) allows the isolation of single crystals of [Ni₂(H₂daps)₂] · CH₂Cl₂ 4 and [Ni₂(H₂daps)₂(CH₃OH)₂] · 3 CH₃OH · H₂O 5 , suitable for X‐ray diffraction studies. Recrystallisation of 4 from pyridine yields [Ni₂(H₂daps)₂(py)₂] · CH₂Cl₂ 6 , previously characterised by us. This study shows the versatility of the H₄daps ligand and the influence that the crystallisation solvent can have on the crystal structure of these complexes.