Mamoun M. Bader

Amyloid-β (Aβ) aggregation and associated structural changes are central features of Alzheimer’s disease (AD) pathology. In this study, we investigated the binding of α-halogenated curcumins, α-bromocurcumin and α-chlorocurcumin, to Aβ_1-42 and examined their effects on the peptide secondary structure using fluorescence spectroscopy and circular dichroism (CD). Both α-halogenated curcumins interacted with Aβ_1-42, but their binding properties differed from those of the parent curcumin. α-Chlorocurcumin exhibited a higher binding affinity for Aβ_1-42 than curcumin, whereas α-bromocurcumin showed comparatively weaker binding. Temperature-dependent binding studies revealed that the association of α-halogenated curcumins with Aβ_1-42 was influenced by temperature, with reduced binding affinity at higher temperatures. Thermodynamic analysis demonstrated favorable free-energy changes for the interactions and revealed that α-halogenation altered the relative enthalpic and entropic contributions to Aβ_1-42 binding. CD analysis further showed that binding of the curcumin altered the secondary structure of Aβ_1-42. These structural changes were more pronounced in the presence of the α-halogenated derivatives, indicating that halogen substitution influences the interaction and conformational response of Aβ_1-42. Molecular docking analysis provided additional insight into the possible binding modes and predicted intermolecular contacts between the α-halogenated curcumin and Aβ_1-42. Overall, the findings demonstrate that α-halogenation modulates the binding and structural effects of curcumin derivatives on Aβ_1-42, with α-chlorocurcumin exhibiting particularly favorable binding characteristics. These findings provide a basis for further investigation of α-halogenated curcumins as potential modulators of Aβ-related molecular processes associated with AD.

Dicyanovinyl (DCV) oligothiophenes are interesting materials due to their unique optical and electronic properties. They are relatively easy to prepare using Knoevenagel condensation reactions from the corresponding aldehydes. Understanding their optical and electrochemical characteristics is important for both building structure/property relationships and for optimizing their performance in various applications. We report on the electrochemical and photophysical properties of three oligothiophenes end-capped with dicyanovinyl -CH=C(CN)₂ or DCV groups. The compounds included in this study are DCV-T-DCV (1), DCV-2T-DCV (2), and DCV-3T-DCV (3), where T represents one thiophene unit. Introduction of the DCV groups into oligothiophenes results in unique evolution of their electrochemical and optical behavior. First, new reversible two-electron reduction processes in the series DCV-nT-DCV start to appear with a gradual increase in the reduction potential with an increasing number of thiophene units. This was consistent with the electronic spectroscopic results. These results demonstrate that the DCV groups can be used in molecular design and fine-tuning of the optical and redox properties of oligothiophene and presumably this strategy can be extended to other conjugated organic molecules. We also report on the photophysical and vibrational spectroscopic properties of these compounds. The C=C stretching bands in Raman and IR spectra reveal more quinoidal nature in shorter molecules and more dominant benzoidal character in longer molecules. The DCV-induced modulation of electrochemical, optical, and vibrational properties highlights their potential in diverse optoelectronic applications.

A reference is added to the article by Pham & Bader [IUCrData (2025), 10, x241243]

Oligothiophenes constitute an important class of conjugated organic materials with unique optical and electrical properties. These properties not only depend on the molecular structure but also on solid-state packing. In this highlight, we summarize the results of our work on the synthesis and crystal structures of a series of oligothiophenes endowed with strong electron accepting groups, namely the dicyanovinyl (DCV) and tricyanovinyl (TCV) groups. We focus on the impact of the presence of these strong electron-accepting groups on the solid-state structures and the dominant inter- and intra-molecular interactions in these materials. The main features observed in these studies include the role of intramolecular CN⋯S interactions in enforcing molecular planarity while promoting π-stack formation, presumably by depleting electron density in the parent compounds. Additionally, some crystals were found to exhibit syn-conformations of sulfur atoms, a feature that is rare in oligothiophenes. We further examine the impact of the presence of molecular structural modifications commonly employed in thiophene chemistry, such as the introduction of vinylene bridges, ethylenedioxy groups or EDOT; bromo- and solubilizing alkyl groups, on solid-state packing motifs. The evolution and modulation of inter- and intra-molecular interactions upon such molecular modification can lead to a better understanding of their role in the observed properties of both oligomers and the corresponding polymers. Seventeen structurally related oligothiophenes, endowed with electron accepting groups, are included in this highlight. We will also briefly discuss how these groups influence the optical, vibrational, and electrochemical properties of these compounds as these are important properties for the development of optical, Raman and electrochemical sensors for biological and environmental applications.

The title compound [systematic name: 4-chloro-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one], C₂₁H₁₉ClO₆, is close to planar, with a dihedral angle of 2.61 (7)° between the terminal phenyl groups and three intramolecular O—H...O hydrogen bonds occur. In the crystal, the molecules are linked into [201] chains by O—H...O hydrogen bonds and weak aromatic π–π stacking is also observed with a shortest centroid–centroid separation of 3.7279 (8) Å.

α- or 4-Substituted curcumin analogues are scarce. We describe herein the syntheses and crystal structures of the first α-halogenated curcumin derivatives: (1E,6E)-1,7-bis (4-hydroxy-3-methoxyphenyl)-4-bromo-5-hydroxy-1,3,6-heptatriene-3-one or (4-bromocurcumin) (1) and (1E,6E)-1,7-bis (4-hydroxy-3-methoxyphenyl)-4-chloro-5-hydroxy-1,3,6-heptatriene-3-one or (4-chlorocurcumin) (2). We note that the key step in the successful synthesis of the bromo-analog is the use of slightly acidic media to favor the diketo form of curcumin prior to carrying out the reaction. Both newly prepared compounds assume the keto–enol form in the solid state and crystallize in the monoclinic space group P2₁/c with four molecules in the unit cell each with slightly different dimensions. Inter- and intra- molecular hydrogen bonds were observed in the two structures. Most significant observed features were the inter-molecular O…O distances of 2.842 and 2.840 Å and intra-molecular O…O distances of 2.460 and 2.451 Å for bromo-or (1) and chloro- or (2) derivatives, respectively. No close halogen…halogen contacts were observed in either of the two structures. Both molecules are nearly planar with torsion angles of 0.54 and 1.16 °C between the planes of two terminal phenyl groups for (1) and (2), respectively. π-Stacks were observed in both structures with interplanar distances of 3.367 and 3.454 Å for the bromo- and chloro- compounds, respectively. Hirshfeld surface analysis confirms quantitively a picture of the inter- and intra-molecular interactions in both compounds compared with polymorph I (the most common form) of curcumin. UV–Vis absorption spectra are shifted to higher wavelengths with l_max of 475 and 477 nm for compounds 1 and 2, respectively, compared with 442 nm in dichloromethane solutions. The newly synthesized molecules will open the door for numerous possible synthetic modifications of the α-carbon to prepare valuable analogues of curcumin with more favorable solubility profiles.

The title compound, C₂₂H₁₂N₂S₂, crystallizes in space group P2₁/c with four molecules in the asymmetric unit. The heterocyclic molecule is quasi-planar with a dihedral angle between the phenyl rings on the periphery of the molecule of 1.73 (19)°. Short H...S (2.92 Å) and C—H...π [2.836 (3) Å] contacts are observed in the crystal with shorted π–π stacking distances of 3.438 (3) Å along the b axis. Surprisingly, and unlike a closely related material, this molecule readily forms large crystals by sublimation and by slow evaporation from dichloromethane. The maximum absorbance in the UV-Vis spectrum is at 533 nm. Emission was measured upon excitation at 533 nm with a fluorescence λ_max of 658 nm and cutoff of 900 nm.

In the title compound, C22H11N3O3S, dihedral angle between the phenyl rings on the periphery of the molecule is 8.05 (18)°. In the crystal, aromatic π–π stacking distance and short C—H⋯O contacts are observed. The maximum absorption occurs at 688 nm.

The title compound, C₂₅H₁₈N₄, crystallizes in the centrosymmetric orthorhombic space group Pbca, with eight molecules in the unit cell. The main feature noticeable in the structure is the impact of the tricyanovinyl (TCV) group in forcing partial planarity of the portion of the molecule carrying the TCV group and directing the molecular packing in the solid state, resulting in the formation of π-stacks of dimers within the unit cell. Short π–π stack closest atom-to-atom distances of 3.444 (15) Å are observed. Such motif patterns are favorable as they are thought to be conducive for better charge transport in organic semiconductors, which results in enhanced device performance. Intramolecular charge transfer is evident from the shortening in the observed experimental bond lengths. The nitrogen atoms (of the cyano groups) are involved in extensive short contacts, primarily through C—H...NC interactions with distances of 2.637 (17) Å.