Synthesis, functionalization and photo-Bergman chemistry of enediyne bioconjugates

LaBeaume, Paul; Wager, Krista; Falcone, Danielle; Li, Jane; Torchilin, Vladimir P.; Castro, Curtis; Holewa, Coleen; Kallmerten, Amy E.; Jones, Graham B.

doi:10.1016/j.bmc.2009.07.059

Cited by 12 publications

(8 citation statements)

References 17 publications

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“…All reagents and solvents were purchased from commercial suppliers and used without further purification. 4-Ethynyl- N , N -dimethylbenzenamine was prepared analogously to published procedures. , While 1 and 2 have been previously described, 3 is unknown to the literature. Anhydrous solvents were prepared by filtration through drying columns.…”

Section: Methodsmentioning

confidence: 99%

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Ethyne-Linked Push–Pull Chromophores: Implications of Crystal Structure and Molecular Electronics on the Quadric Nonlinear Activity

Kautny

Kriegner

Bader

et al. 2017

Crystal Growth & Design

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Three ethyne-linked push–pull materials consisting of a dimethylaniline donor and acceptors of increasing electron-withdrawing strength were prepared as nonlinear optical chromophores. Despite a high similarity of the molecular structures, all three materials featured unrelated non-centrosymmetric crystallization behavior. One of the compounds exhibits a remarkable packing with Z′ = 16 molecules in the asymmetric unit forming two interpenetrating subsystems. Inspection of the nonlinear optical activity of single crystalline powders revealed an extraordinarily efficient second harmonic generation of one of the materials with a 1200-fold increased second harmonic response compared to potassium dihydrogen phosphate. The second harmonic generation efficiency of the materials under investigation has been related to both the intrinsic molecular properties as well as the alignment of the individual chromophores within the crystal packing, highlighting the importance of a multidisciplinary approach to understand the properties of nonlinear optical materials.

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Section: Methodsmentioning

confidence: 99%

“…4-Ethynyl-N,N-dimethylbenzenamine was prepared analogously to published procedures. 28,29 While 1 30 and 2 31 have been previously described, 3 is unknown to the literature. Anhydrous solvents were prepared by filtration through drying columns.…”

Section: ■ Introductionmentioning

confidence: 99%

Ethyne-Linked Push–Pull Chromophores: Implications of Crystal Structure and Molecular Electronics on the Quadric Nonlinear Activity

Kautny

Kriegner

Bader

et al. 2017

Crystal Growth & Design

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“…In the case of an enediynyl pentapeptide synthesized by Basak et al, the fluorescence quantum yield of the molecule is enhanced in the presence of gold nanoparticles in polar organic solvent due to the interaction between the gold surface and nitrogen lone pair, which otherwise donates into the photoexcited π-system . In another example, room temperature solution stability can be greatly enhanced for asymmetric carbon-framework enediynes by incubating them with gold nanoparticles. , In contrast, Mondal et al showed that DNA cleavage reactivity of simple dithiol enediynes under UV excitation or thermal incubation was increased by upward of 50% using gold nanoparticles, possibly due to a surface concentration effect …”

Section: Photoelectronic and Photothermal Enediyne Activation At Expa...mentioning

confidence: 99%

The Outliers: Metal-Mediated Radical Reagents for Biological Substrate Degradation

2019

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Conspectus The predictable and controllable interaction of small organic or peptidic molecules with biological substrates is the primary reason most pharmaceuticals are narrowly decorated carbon frameworks. The inhibition or activation binding models are measurable and without side reactions that can cause pathological angst. Yet many diseases, especially those involving rapid proliferation of cells (i.e., cancer) or aggregation of peptides (e.g., heart disease, Alzheimer’s disease) have not yet been cured by inhibition therapeutics. Additionally, interventional medicine is often required to alleviate such maladies by physical removal first, followed by molecular-level therapy as a second stage. Thus, there appears to be a niche for more aggressive therapeutics that may employ harsher chemical processes to realize clinical efficacy, albeit without causing catastrophic side effects. Molecules that may be considered for this challenge are not typically biomimetic, nor do they fit the traditional pharmaceutical paradigm. They may have unusual modes of action or undesired reactivity that can be lethal if not controlled. These are the outliers; potential pharmacophores that biology does not know how to manage or adapt to. This is why they may be an intriguing class of agents that needs continuous development. In this Account, we connect the under-developed enediyne family of compounds and our metalloenediyne derivatives to existing radical-based therapeutics such as bleomycin and doxorubicin to illustrate that controlled diradical reactivity, although an outlier mechanism, has a place in the therapeutic portfolio. This is self-evident in that of the 11 natural product enediynes known, 2 have clinical impact, a strong ratio. We expand on the chemical diversity of potential enediyne constructs and focus on the accessible trigger mechanisms to activate diradical formation as a method to control toxicity. Moreover, we further illustrate how electromagnetic fields can be employed to activate both molecular and larger nanomaterial constructs that carry highly concentrated payloads of reactive reagent. Finally, we describe how controlled diradical reactivity can reach beyond traditional therapeutic targets such as DNA, to peptide aggregates found in blood clots, neural fibrils, and membrane scaffolds. It is our belief that cleverly constructed frameworks with well-designed and controlled activation/reaction schemes can lead to novel therapeutics that can challenge evolving viral and bacterial invaders. From this evangelical perspective, our hope is that the conceptual framework, if not the specific designs in this Account, stimulate the readership to develop out-of-the-box therapeutic designs that may combat resistant disease targets.

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“…12 The o-xylene derived bisacetylene substrate (1b) was synthesized analogously. 13 The compounds 1 were then reacted with the boranes 2.…”

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confidence: 99%

1,1-Carboboration Route to Substituted Naphthalenes

et al. 2012

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Synthesis, functionalization and photo-Bergman chemistry of enediyne bioconjugates

Cited by 12 publications

References 17 publications

Ethyne-Linked Push–Pull Chromophores: Implications of Crystal Structure and Molecular Electronics on the Quadric Nonlinear Activity

Ethyne-Linked Push–Pull Chromophores: Implications of Crystal Structure and Molecular Electronics on the Quadric Nonlinear Activity

The Outliers: Metal-Mediated Radical Reagents for Biological Substrate Degradation

1,1-Carboboration Route to Substituted Naphthalenes

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