Characterization of pyridinylimine and pyridinylmethylamine derivatives and their corresponding metal complexes

Braymer, Joseph J.; Merrill, Nathan; Lim, Mi Hee

doi:10.1016/j.ica.2011.08.056

Cited by 16 publications

(25 citation statements)

References 37 publications

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“…3). 10 f ,10 h - l ,10 o ,10 p ,26 The primary amine common to all four aminoisoflavones was assigned to the most acidic p K a values, consistent with the predicted values for these structures. 27 Deprotonation of the ammonium (RNH 3 + ) to the primary amine (RNH 2 ) was represented by p K a values of 1.3 ± 0.1 for 1 , 1.8 ± 0.5 for 2 , 2.2 ± 0.9 for 3 , and 1.5 ± 0.4 for 4 .…”

Section: Resultssupporting

confidence: 77%

“…4). 10 f ,10 h ,10 j - l ,10 o ,10 p ,26 Based on the calculated log β values, a solution speciation diagram was generated and indicated a mixture of Cu(II)– 4 complexes in 1:1 and 1:2 Cu(II)/ligand ratios. As depicted in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…, pCu = −log[Cu(II) unchelated ]). 10 f ,10 h ,10 k ,10 l ,10 o ,10 p ,26 At pH 7.4, which was used for the in vitro experiments and is physiologically relevant, the pCu value for 4 was ca. 17, suggesting an estimated K d for Cu(II)– 4 in the lower femtomolar range.…”

Section: Resultsmentioning

confidence: 99%

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Interaction and reactivity of synthetic aminoisoflavones with metal-free and metal-associated amyloid-β

et al. 2014

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Metal ion homeostasis in conjunction with amyloid-β (Aβ) aggregation in the brain has been implicated in Alzheimer’s disease (AD) pathogenesis. To uncover the interplay between metal ions and Aβ peptides, synthetic, multifunctional small molecules have been employed to modulate Aβ aggregation in vitro. Naturally occurring flavonoids have emerged as a valuable class of compounds for this purpose due to their ability to modulate both metal-free and metal-induced Aβ aggregation. Although, flavonoids have shown anti-amyloidogenic effects, the structural moieties of flavonoids responsible for such reactivity have not been fully identified. In order to understand the structure-interaction-reactivity relationship within the flavonoid family for metal-free and metal-associated Aβ, we designed, synthesized, and characterized a set of isoflavone derivatives, aminoisoflavones (1-4), that displayed reactivity (i.e., modulation of Aβ aggregation) in vitro. NMR studies revealed a potential binding site for aminoisoflavones between the N-terminal loop and central helix on prefibrillar Aβ different from the non-specific binding observed for other flavonoids. The absence or presence of the catechol group differentiated the binding affinities and enthalpy/entropy balance between aminoisoflavones and Aβ. Furthermore, having a catechol group influenced the binding mode with fibrillar Aβ. Inclusion of additional substituents moderately tuned the impact of aminoisoflavones on Aβ aggregation. Overall, through these studies, we obtained valuable insights on the requirements for parity among metal chelation, intermolecular interactions, and substituent variation for Aβ interaction.

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Section: Resultssupporting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

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Interaction and reactivity of synthetic aminoisoflavones with metal-free and metal-associated amyloid-β

et al. 2014

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“…When 1 equiv of ZnCl 2 was introduced in a solution of DPP1 or DPP2 (in CD 3 CN), noticeable downfield chemical shifts of the pyridyl protons were recorded (Figure 3b), demonstrating that Zn 2+ binding to the ligand occurred through the pyridyl N-donor atom. 46 Overall, both UV-Vis and NMR studies confirmed Cu 2+ or Zn 2+ binding to DPP1 and DPP2 .…”

Section: Resultsmentioning

confidence: 78%

“…28–33, 46 A solution of ligand (20 µM in EtOH) was prepared, treated with 1 to 20 equiv of CuCl 2 , and incubated at room temperature for 2.5 h (for DPP1 ) or 5 min (for DPP2 ). The optical spectra of the resulting solutions were measured by UV-Vis.…”

Section: Methodsmentioning

confidence: 99%

Reactivity of Diphenylpropynone Derivatives Toward Metal-Associated Amyloid-β Species

et al. 2012

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In Alzheimer’s disease (AD), metal-associated amyloid-β (metal–Aβ) species have been suggested to be involved in neurotoxicity; however, their role in disease development is still unclear. To elucidate this aspect, chemical reagents have been developed as valuable tools for targeting metal–Aβ species, modulating the interaction between the metal and Aβ, and subsequently altering metal–Aβ reactivity. Herein, we report the design, preparation, characterization, and reactivity of two diphenylpropynone derivatives (DPP1 and DPP2) composed of structural moieties for metal chelation and Aβ interaction (bifunctionality). The interactions of these compounds with metal ions and Aβ species were confirmed by UV-Vis, mass spectrometry, and docking studies. The effects of these bifunctional molecules on the control of in vitro metal-free and metal-induced Aβ aggregation were investigated and monitored by gel electrophoresis and transmission electron microscopy (TEM). Both DPP1 and DPP2 showed reactivity toward metal–Aβ species over metal-free Aβ species to different extents. In particular, DPP2, which contains a dimethylamino group, exhibited greater reactivity with metal–Aβ species than DPP1, suggesting a structure-reactivity relationship. Overall, our studies present a new bifunctional scaffold that could be utilized to develop chemical reagents for investigating metal–Aβ species in AD.

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Copper(II) Complexes Containing N,N′‐Bidentate N‐(Pyridin‐2‐ylmethyl)aniline and Its Derivatives: Synthesis, Structure and Magnetic Property

Ahn

Lee

2015

Bulletin Korean Chem Soc

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New Cu(II) complexes, dinuclear [CuLb(μ‐Cl)Cl]2 and monomeric [CuLcCl2], along with polynuclear [CuLaCl2]n for comparison, were prepared and characterized using X‐ray crystallography. Variable‐temperature (2−300 K) magnetic susceptibility (χ) data of [CuLaCl2]n and [CuLb(μ‐Cl)Cl]2 showed weak antiferromagnetic interactions through the bridged chlorido groups within the polymeric and dimeric units, respectively.

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Characterization of pyridinylimine and pyridinylmethylamine derivatives and their corresponding metal complexes

Cited by 16 publications

References 37 publications

Interaction and reactivity of synthetic aminoisoflavones with metal-free and metal-associated amyloid-β

Interaction and reactivity of synthetic aminoisoflavones with metal-free and metal-associated amyloid-β

Reactivity of Diphenylpropynone Derivatives Toward Metal-Associated Amyloid-β Species

Copper(II) Complexes Containing N,N′‐Bidentate N‐(Pyridin‐2‐ylmethyl)aniline and Its Derivatives: Synthesis, Structure and Magnetic Property

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