Mechanochemical Synthesis of New Praziquantel Cocrystals: Solid-State Characterization and Solubility.

New cocrystals of praziquantel with suberic, 3-hydroxybenzoic, benzene-1,2,4,5-tetracarboxylic, trimesic, and 5-hydroxyisophthalic acids were obtained through ball milling experiments. The optimal conditions for the milling process were chosen by changing the solvent volume and the mechanical action time. Supramolecular interactions in the new cocrystals are detailed based on single-crystal X-ray diffraction analysis, confirming the expected formation of hydrogen bonds between the praziquantel carbonyl group and the carboxyl (or hydroxyl) moieties of the coformers.

Comparing Prognosis for , , and Non-BRCA Breast Cancer.

Background: Germline pathogenic variants (PV) in and genes, which account for 20% of familial breast cancer (BC) cases, are highly penetrant and are associated with Hereditary Breast/Ovarian Cancer Syndrome. Previous studies, mostly including higher numbers of BC patients, yielded conflicting results regarding BC outcomes. In the Portuguese population, BC is diagnosed more frequently than BC.

Structural Optimization of Antimycobacterial Azaaurones Towards Improved Solubility and Metabolic Stability.

While N-acetyl azaaurones have already been disclosed for their potential against tuberculosis (TB), their low metabolic stability remains an unaddressed liability. We now report a study designed to improve the metabolic stability and solubility of the azaaurone scaffold and to identify the structural requirements for antimycobacterial activity. Replacing the N-acetyl moiety for a N-carbamoyl group led to analogues with sub- and nanomolar potencies against M.

Mechanochemistry in Portugal-A Step towards Sustainable Chemical Synthesis.

In Portugal, publications with mechanochemical methods date back to 2009, with the report on mechanochemical strategies for the synthesis of metallopharmaceuticals. Since then, mechanochemical applications have grown in Portugal, spanning several fields, mainly crystal engineering and supramolecular chemistry, catalysis, and organic and inorganic chemistry. The area with the most increased development is the synthesis of multicomponent crystal forms, with several groups synthesizing solvates, salts, and cocrystals in which the main objective was to improve physical properties of the active pharmaceutical ingredients.

Hereditary breast cancer and ancestry in the Madeira archipelago: an exploratory study.

Access to genetic testing and counselling in remote areas such as the Madeira archipelago, in the Northern Atlantic Ocean, may be complex. Different counselling methods, including telegenetics, should be explored. In this study, we characterise the Hereditary Breast/Ovarian Cancer (HBOC) families with Madeira ancestry enrolled in our programme.

Antimicrobial Activity of Pyrazinamide Coordination Frameworks Synthesized by Mechanochemistry.

The urge for the development of a more efficient antibiotic crystalline forms led us to the disclosure of new antibiotic coordination frameworks of pyrazinamide, a well-known drug used for the treatment of tuberculosis, with some of the novel compounds unravelling improved antimycobacterial activity. Mechanochemistry was the preferred synthetic technique to yield novel compounds, allowing the reproduction of a 1D zinc framework, the synthesis of a novel hydrogen bonding manganese framework, and three new compounds with silver. The structural characterization of the novel forms is presented along with stability studies.

The Lisbon Supramolecular Green Story: Mechanochemistry towards New Forms of Pharmaceuticals.

This short review presents and highlights the work performed by the Lisbon Group on the mechanochemical synthesis of active pharmaceutical ingredients (APIs) multicomponent compounds. Here, we show some of our most relevant contributions on the synthesis of supramolecular derivatives of well-known commercial used drugs and the corresponding improvement on their physicochemical properties. The study reflects, not only our pursuit of using crystal engineering principles for the search of supramolecular entities, but also our aim to correlate them with the desired properties.

Silica nanocarriers with user-defined precise diameters by controlled template self-assembly.

Mesoporous silica nanoparticles (MSNs) feature ideal structural properties and surface chemistry for use as nanocarriers of molecules, polymers and biomolecules in cutting-edge applications. One important challenge remaining in their preparation is the ability to tune their diameter in the range of a few tens of nanometers, with narrow size dispersity, preferably using a simple, sustainable and scalable synthetic process. This work presents a fully controllable low-temperature and purely aqueous sol-gel method to prepare MSNs with user-defined diameters from 15 nm to 80 nm and narrow size dispersity.

Targeting leucine-rich repeat kinase 2 (LRRK2) for the treatment of Parkinson's disease.

Leucine-rich repeat kinase 2 (LRRK2) is a serine-threonine kinase involved in multiple cellular processes and signaling pathways. mutations are associated with autosomal-inherited Parkinson's disease (PD), and evidence suggests that LRRK2 pathogenic variants generally increase kinase activity. Therefore, inhibition of LRRK2 kinase function is a promising therapeutic strategy for PD treatment.

Cucurbalsaminones A-C, Rearranged Triterpenoids with a 5/6/3/6/5-Fused Pentacyclic Carbon Skeleton from , as Multidrug Resistance Reversers.

Three new triterpenoids, cucurbalsaminones A-C (-), featuring a unique 5/6/3/6/5-fused pentacyclic carbon skeleton, named cucurbalsaminane, were isolated from a methanol extract of . Their structures were elucidated by spectroscopic methods and corroborated, for , by structure solution using single-crystal X-ray diffraction analysis. A hypothetical biogenetic pathway for these compounds is proposed.

Mg- and Mn-MOFs Boost the Antibiotic Activity of Nalidixic Acid.

The development of metal-organic frameworks (MOFs) enclosing active pharmaceutical ingredients is of considerable interest, as their use in controlled drug release and delivery is very promising. Although nalidixic acid is an antibiotic with a broad spectrum of biological applications, effective mainly against Gram-negative infections, its oral bioavailability is low due to a poor solubility and slow dissolution. Herein, we report new metal-organic frameworks (BioMOFs) comprising nalidixic acid and divalent magnesium and manganese ions.

Hydrogen bonding networks in gabapentin protic pharmaceutical salts: NMR and in silico studies.

Hydrogen bonds (HBs) play a key role in the supramolecular arrangement of crystalline solids and, although they have been extensively studied, the influence of their strength and geometry on crystal packing remains poorly understood. Here we describe the crystal structures of two novel protic gabapentin (GBP) pharmaceutical salts prepared with the coformers methanesulfonic acid (GBP:METHA) and ethanesulfonic acid (GBP:ETHA). This study encompasses experimental and computational electronic structure analyses of H NMR chemical shifts (CSs), upon in silico HB cleavage.

Ionic Co-Crystal Formation as a Path Towards Chiral Resolution in the Solid State.

The preparation and characterization of a whole family of hydrated ionic co-crystals formed by both enantiopure l-proline and racemic dl-proline with LiX (X=Cl, Br, I) are reported. The chiral preference of the lithium cation for homochiral coordination, both in the formation of crystalline conglomerates (with Cl and Br) and racemates (with Cl and I), in which molecules of opposite chirality are confined to distinct crystal layers, is discussed. Dehydration processes for all hydrated crystals have also been investigated.

Exploring mechanochemistry to turn organic bio-relevant molecules into metal-organic frameworks: a short review.

Mechanochemistry is a powerful and environmentally friendly synthetic technique successfully employed in different fields of synthetic chemistry. Application spans from organic to inorganic chemistry including the synthesis of coordination compounds. Metal-organic frameworks (MOFs) are a class of compounds with numerous applications, from which we highlight herein their application in the pharmaceutical field (BioMOFs), whose importance has been growing and is now assuming a relevant and promising domain.

MechanoAPI-ILs: Pharmaceutical Ionic Liquids Obtained through Mechanochemical Synthesis.

An alternative, efficient, and green synthetic strategy for the preparation of pharmaceutical ionic liquids using mechanochemistry (MechanoAPI-ILs) is reported. Six new API-ILs based on gabapentin and l-glutamic acid were successfully synthesized and characterized, demonstrating that mechanochemistry is a very promising synthetic strategy. Results compare both the new and the classical approach and clearly show the advantages of the new method.

12,17-Cyclojatrophane and Jatrophane Constituents of Euphorbia welwitschii.

Euphowelwitschines A (1) and B (2), isolated from a methanolic extract of Euphorbia welwitschii, exhibit a rare combination of structural features in having a 5/8/8 fused-ring system and a 12,15-ether bridge. Moreover, the isolation of the additional new compounds welwitschene (3) and epoxywelwitschene (4) has provided insights into the biogenetic pathway of 12,17-cyclojatrophanes. The structures of 1-4 were determined by spectroscopic methods inclusive of 1D and 2D NMR experiments and X-ray crystallography for compounds 1 and 2.

Luminescent Di- and Trinuclear Boron Complexes Based on Aromatic Iminopyrrolyl Spacer Ligands: Synthesis, Characterization, and Application in OLEDs.

New bis- and tris(iminopyrrole)-functionalized linear (1,2-(HNC4 H3 -C(H)N)2 -C6 H4 (2), 1,3-(HNC4 H3 -C(H)N)2 -C6 H4 (3), 1,4-(HNC4 H3 -C(H)N)2 -C6 H4 (4), 4,4'-(HNC4 H3 -C(H)N)2 -(C6 H4 -C6 H4 ) (5), 1,5-(HNC4 H3 C-(H)N)2 -C10 H6 (6), 2,6-(HNC4 H3 C-(H)N)2 -C10 H6 (7), 2,6-(HNC4 H3 C-(H)N)2 -C14 H8 (8)) and star-shaped (1,3,5-(HNC4 H3 -C(H)N-1,4-C6 H4 )3 -C6 H3 (9)) π-conjugated molecules were synthesized by the condensation reactions of 2-formylpyrrole (1) with several aromatic di- and triamines. The corresponding linear diboron chelate complexes (Ph2 B[1,3-bis(iminopyrrolyl)-phenyl]BPh2 (10), Ph2 B[1,4-bis(iminopyrrolyl)-phenyl]BPh2 (11), Ph2 B[4,4'-bis(iminopyrrolyl)-biphenyl]BPh2 (12), Ph2 B[1,5-bis(iminopyrrolyl)-naphthyl]BPh2 (13), Ph2 B[2,6-bis(iminopyrrolyl)-naphthyl]BPh2 (14), Ph2 B[2,6-bis(iminopyrrolyl)-anthracenyl]BPh2 (15)) and the star-shaped triboron complex ([4',4'',4'''-tris(iminopyrrolyl)-1,3,5-triphenylbenzene](BPh2 )3 (16)) were obtained in moderate to good yields, by the treatment of 3-9 with B(C6 H5 )3 . The ligand precursors are non-emissive, whereas most of their boron complexes are highly fluorescent; their emission color depends on the π-conjugation length.

Dicarboxylate recognition properties of a dinuclear copper(II) cryptate.

A ditopic polyamine macrobicyclic compound with biphenylmethane spacers was prepared, and its dinuclear copper(II) complex was studied as a receptor for the recognition of dicarboxylate anions of varying chain length in H2O/MeOH (50:50 (v/v)) solution. The acid-base behavior of the compound, the stability constants of its complexes with Cu(2+) ion, and the association constants of the copper(II) cryptate with succinate (suc(2-)), glutarate (glu(2-)), adipate (adi(2-)), and pimelate (pim(2-)) were determined by potentiometry at 298.2 ± 0.

Sulfate recognition by a hexaaza cryptand receptor.

A hexamine macrobicycle with pyrrolyl spacers was evaluated as an anion receptor in its protonated forms. The protonation constants of the receptor, as well as its association constants with Cl(-), NO3(-), AcO(-), ClO4(-), H2PO4(-), and SO4(2-) were determined by potentiometry at 298.2 ± 0.

Trienamines derived from 5-substituted furfurals: remote ε-functionalization of 2,4-dienals.

The selective ε-functionalization of 5-substituted furfurals via trienamine intermediates is reported herein. This methodology was successfully applied to several 5-substituted furfurals with different amines via formation of a trienamine through the furan ring. The rationalized reaction mechanism involves the addition of the trienamine intermediate to its corresponding iminium-ion producing new furan-containing scaffolds.

Tunable fluorophores based on 2-(N-arylimino)pyrrolyl chelates of diphenylboron: synthesis, structure, photophysical characterization, and application in OLEDs.

Reactions of 2-(N-arylimino)pyrroles (HNC4H3C(H)=N-Ar) with triphenylboron (BPh3) in boiling toluene afford the respective highly emissive N,N'-boron chelate complexes, [BPh2 {κ(2)N,N'-NC4H3C(H)=N-Ar}] (Ar=C6H5 (12), 2,6-Me2-C6H3 (13), 2,6-iPr2-C6H3 (14), 4-OMe-C6H4 (15), 3,4-Me2-C6 H3 (16), 4-F-C6H4 (17), 4-NO2-C6H4 (18), 4-CN-C6H4 (19), 3,4,5-F3-C6H2 (20), and C6F5 (21)) in moderate to high yields. The photophysical properties of these new boron complexes largely depend on the substituents present on the aryl rings of their N-arylimino moieties. The complexes bearing electron-withdrawing aniline substituents 17-20 show more intense (e.

Toward the understanding of radical reactions: experimental and computational studies of titanium(III) diamine bis(phenolate) complexes.

Radical reactions of titanium(III) [Ti((tBu2)O2NN')Cl(S)] (S = THF, 1; S = py, 2; (tBu2)O2NN' = Me2N(CH2)2N(CH2-2-O-3,5-(t)Bu2C6H2)2) are described. Reactions with neutral electron acceptors led to metal oxidation to Ti(IV), [Ti((tBu2)O2NN')Cl(TEMPO)] (4) being formed with the TEMPO radical and [Ti((tBu2)O2NN')Cl2] (9) with PhN═NPh. [Ti((tBu2)O2NN')Cl2] was also formed when [Ti((tBu2)O2NN')Cl(S)] was oxidized by [Cp2Fe][BPh4], but the [Cp2Fe][PF6] analogue yielded [Ti((tBu2)O2NN')ClF] (8).

N-heterocyclic carbene catalyzed addition of aldehydes to diazo compounds: stereoselective synthesis of N-acylhydrazones.

An innovative stereoselective synthesis of N-acylhydrazones via an unprecedented N-heterocyclic carbene catalyzed addition of aldehydes to diazo compounds is presented. Enals exclusively afforded N-acylhydrazones, in yields up to 91%. The observed regioselectivity was traced back to the reaction of the vinylogous Breslow intermediate via the acyl anion pathway over competing homoenolate, enol, and acyl azolium pathways.