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Journal of Computational Chemistry Apr 2024Using density functional theory (DFT), we treat the reaction of coupling of CO with aziridine in gas phase, in the presence of water and of a green catalyst (NaBr)....
Using density functional theory (DFT), we treat the reaction of coupling of CO with aziridine in gas phase, in the presence of water and of a green catalyst (NaBr). Computations show that, in gas phase, this ring-opening conversions to oxazolidinones initiates by coordinating a CO molecule to the nitrogen atom of the aziridine. Then, a nucleophilic interaction between one oxygen atom of the coordinated CO and the carbon atom of the aziridine occurs. For methyl substituted aziridine, two pathways are proposed leading either to 4-oxazolidinone or to 5-oxazolidinone. Besides, we show that the activation energy of this reaction reduces in aqueous solution, in the presence of a water molecule explicitly or NaBr catalyst. In addition, the corresponding reaction mechanisms and regioselectivity associated with this ring-opening conversions to oxazolidinones, in the presence of carbon dioxide are found to be influenced by solvent and catalyst. The present findings should allow better designing regioisomer oxazolidinones relevant for organic chemistry, medicinal and pharmacological applications.
PubMed: 38031324
DOI: 10.1002/jcc.27270 -
Chemical Communications (Cambridge,... Jul 2023A new type of metal-free [5+1] cycloaddition reaction of donor-acceptor aziridines with 2-(2-isocyanoethyl)indoles is reported herein. This method exhibits broad...
A new type of metal-free [5+1] cycloaddition reaction of donor-acceptor aziridines with 2-(2-isocyanoethyl)indoles is reported herein. This method exhibits broad substrate scope and atom-economy. A series of 2-1,4-oxazines containing an indole heterocycle skeleton were obtained in up to 92% yield under mild reaction conditions. Control experiments revealed that free indole N-H is crucial for the above transformations. The theoretical calculation studies provided guidance on the in-depth insight into the reaction mechanism and the hydrogen-bond between the free indole N-H and carbonyl group was identified to lower the free energy barrier in the transition states.
Topics: Oxazines; Cycloaddition Reaction; Aziridines; Metals
PubMed: 37338511
DOI: 10.1039/d3cc02193a -
Cells Jul 2023Tumor therapy escape due to undesired side effects induced by treatment, such as prosurvival autophagy or cellular senescence, is one of the key mechanisms of resistance...
Tumor therapy escape due to undesired side effects induced by treatment, such as prosurvival autophagy or cellular senescence, is one of the key mechanisms of resistance that eventually leads to tumor dormancy and recurrence. Glioblastoma is the most frequent and practically incurable neoplasm of the central nervous system; thus, new treatment modalities have been investigated to find a solution more effective than the currently applied standards based on temozolomide. The present study examined the newly synthesized compounds of aziridine-hydrazide hydrazone derivatives to determine their antineoplastic potential against glioblastoma cells in vitro. Although the output of our investigation clearly demonstrates their proapoptotic activity, the cytotoxic effect appeared to be blocked by treatment-induced autophagy, the phenomenon also detected in the case of temozolomide action. The addition of an autophagy inhibitor, chloroquine, resulted in a significant increase in apoptosis triggered by the tested compounds, as well as temozolomide. The new aziridine-hydrazide hydrazone derivatives, which present cytotoxic potential against glioblastoma cells comparable to or even higher than that of temozolomide, show promising results and, thus, should be further investigated as antineoplastic agents. Moreover, our findings suggest that the combination of an apoptosis inducer with an autophagy inhibitor could optimize chemotherapeutic efficiency, and the addition of an autophagy inhibitor should be considered as an optional adjunctive therapy minimizing the risk of tumor escape from treatment.
Topics: Humans; Glioblastoma; Temozolomide; Chloroquine; Hydrazones; Hydrazines; Antineoplastic Agents; Autophagy; Aziridines
PubMed: 37508570
DOI: 10.3390/cells12141906 -
Organic Letters Nov 2023Sc(III)-catalyzed domino C-C and C-N bond formation of -sulfonyl aziridines with quinones has been accomplished to furnish functionalized indolines at a moderate...
Sc(III)-catalyzed domino C-C and C-N bond formation of -sulfonyl aziridines with quinones has been accomplished to furnish functionalized indolines at a moderate temperature. The umpolung reactivity of aziridines, radical pathway, mild reaction conditions, substrate scope, and coupling of drug molecules in a postsynthetic application are the important practical features.
PubMed: 37874042
DOI: 10.1021/acs.orglett.3c03318 -
Chemical Science Nov 2023We report a chiral phosphoric acid catalyzed apparent hydrolytic ring-opening reaction of racemic aziridines in a regiodivergent parallel kinetic resolution manner....
We report a chiral phosphoric acid catalyzed apparent hydrolytic ring-opening reaction of racemic aziridines in a regiodivergent parallel kinetic resolution manner. Harnessing the acyloxy-assisted strategy, the highly stereocontrolled nucleophilic ring-opening of aziridines with water is achieved. Different kinds of aziridines are applicable in the process, giving a variety of enantioenriched aromatic or aliphatic amino alcohols with up to 99% yields and up to >99.5 : 0.5 enantiomeric ratio. Preliminary mechanistic study as well as product elaborations were inducted as well.
PubMed: 37969581
DOI: 10.1039/d3sc03899h -
Current Opinion in Chemical Biology Jun 2024Reactive amino acid side chains play important roles in the binding of peptides to specific targets. In addition, their reactivity enables selective peptide conjugation... (Review)
Review
Reactive amino acid side chains play important roles in the binding of peptides to specific targets. In addition, their reactivity enables selective peptide conjugation and functionalization for pharmaceutical purposes. Diverse reactive amino acids are incorporated into nonribosomal peptides, which serve as a source for drug candidates. Notable examples include (poly)unsaturated (enamine, alkyne, and furyl) and halogenated residues, strained carbacycles (cyclopropyl and cyclopropanol), small heterocycles (oxirane and aziridine), and reactive N-N functionalities (hydrazones, diazo compounds, and diazeniumdiolates). Their biosynthesis requires diverse biocatalysts for sophisticated reaction mechanisms. Several avenues have been identified for their incorporation into peptides, the recruitment by adenylation domains or ligases, on-line modifications, and enzymatic tailoring reactions. Combined with protein engineering approaches, this knowledge provides new opportunities in synthetic biology and bioorthogonal chemistry.
PubMed: 38936328
DOI: 10.1016/j.cbpa.2024.102494 -
Journal of the American Chemical Society Apr 2024Herein, we report that readily accessible azoxy-triazenes can serve as nitrogen atom sources under visible light excitation for the phthalimido-protected aziridination...
Herein, we report that readily accessible azoxy-triazenes can serve as nitrogen atom sources under visible light excitation for the phthalimido-protected aziridination of alkenes. This approach eliminates the need for external oxidants, precious transition metals, and photocatalysts, marking a departure from conventional methods. The versatility of this transformation extends to the selective aziridination of both activated and unactivated multisubstituted alkenes of varying electronic profiles. Notably, this process avoids the formation of competing C-H insertion products. The described protocol is operationally simple, scalable, and adaptable to photoflow conditions. Mechanistic studies support the idea that the photofragmentation of azoxy-triazenes results in the generation of a free singlet nitrene. Furthermore, a mild photoredox-catalyzed N-N cleavage of the protecting group to furnish the free aziridines is reported. Our findings contribute to the advancement of sustainable and practical methodologies for the synthesis of nitrogen-containing compounds, showcasing the potential for broader applications in synthetic chemistry.
PubMed: 38522088
DOI: 10.1021/jacs.3c14713 -
Journal of the American Chemical Society Dec 2023Attaining controllable molecular motion at the nanoscale can be beneficial for multiple reasons, spanning from optoelectronics to catalysis. Here we study the movement...
Attaining controllable molecular motion at the nanoscale can be beneficial for multiple reasons, spanning from optoelectronics to catalysis. Here we study the movement of a two-legged molecular walker by modeling the migration of a phenyl aziridine ring on curved graphene. We find that directional ring migration can be attained on graphene in the cases of both 1D (wrinkled/rippled) and 2D (bubble-shaped) curvature. Using a descriptor approach based on graphene's frontier orbital orientation, we can understand the changes in binding energy of the ring as it translates across different sites with variable curvature and the kinetic barriers associated with ring migration. Additionally, we show that the extent of covalent bonding between graphene and the molecule at different sites directly controls the binding energy gradient, propelling molecular migration. Importantly, one can envision such walkers as carriers of charge and disruptors of local bonding. This study enables a new way to tune the electronic structure of two-dimensional materials for a range of applications.
PubMed: 38049385
DOI: 10.1021/jacs.3c08850 -
Molecules (Basel, Switzerland) May 2024Breast cancer is associated with high mortality and morbidity rates. As about 20-30% of patients exhibiting ER-positive phenotype are resistant to hormonal treatment...
Lactic Acid Bacteria-Derived Postbiotics as Adjunctive Agents in Breast Cancer Treatment to Boost the Antineoplastic Effect of a Conventional Therapeutic Comprising Tamoxifen and a New Drug Candidate: An Aziridine-Hydrazide Hydrazone Derivative.
Breast cancer is associated with high mortality and morbidity rates. As about 20-30% of patients exhibiting ER-positive phenotype are resistant to hormonal treatment with the standard drug tamoxifen, finding new therapies is a necessity. Postbiotics, metabolites, and macromolecules isolated from probiotic bacteria cultures have been proven to have sufficient bioactivity to exert prohealth and anticancer effects, making them viable adjunctive agents for the treatment of various neoplasms, including breast cancer. In the current study, postbiotics derived from and cultures were assessed on an in vitro breast cancer model as potential adjunctive agents to therapy utilizing tamoxifen and a candidate aziridine-hydrazide hydrazone derivative drug. Cell viability and cell death processes, including apoptosis, were analyzed for neoplastic MCF-7 cells treated with postbiotics and synthetic compounds. Cell cycle progression and proliferation were analyzed by PI-based flow cytometry and Ki-67 immunostaining. Postbiotics decreased viability and triggered apoptosis in MCF-7, modestly affecting the cell cycle and showing a lack of negative impact on normal cell viability. Moreover, they enhanced the cytotoxic effect of tamoxifen and the new candidate drug toward MCF-7, accelerating apoptosis and the inhibition of proliferation. This illustrates postbiotics' potential as natural adjunctive agents supporting anticancer therapy based on synthetic drugs.
Topics: Humans; Tamoxifen; Breast Neoplasms; MCF-7 Cells; Female; Aziridines; Apoptosis; Cell Proliferation; Cell Survival; Hydrazones; Probiotics; Antineoplastic Agents; Cell Cycle
PubMed: 38792153
DOI: 10.3390/molecules29102292 -
Inorganic Chemistry Jul 2023The tripodal compounds [(TMGtrphen)M-solv](PF) (M = Mn, Fe, Co; solv = MeCN, DMF) and bipodal analogues [(TMGbiphen)M(NCMe)](PF) ( = 3 for Mn, Fe; = 2 for Co) and...
Cationic Divalent Metal Sites (M = Mn, Fe, Co) Operating as Both Nitrene-Transfer Agents and Lewis Acids toward Mediating the Synthesis of Three- and Five-Membered -Heterocycles.
The tripodal compounds [(TMGtrphen)M-solv](PF) (M = Mn, Fe, Co; solv = MeCN, DMF) and bipodal analogues [(TMGbiphen)M(NCMe)](PF) ( = 3 for Mn, Fe; = 2 for Co) and [(TMGbiphen)MCl] have been synthesized with ligands that feature a triaryl- or diarylmethyl-amine framework and superbasic tetramethylguanidinyl residues (TMG). The dicationic M(II) sites mediate catalytic nitrene-transfer reactions between the imidoiodinane PhI═NTs (Ts = tosyl) and a panel of styrenes in MeCN to afford aziridines and low yields of imidazolines (upon MeCN insertion) with an order of productivity that favors the bipodal over the tripodal reagents and a metal preference of Fe > Co ≥ Mn. In CHCl, the more acidic Fe(II) sites favor formation of 2,4-diaryl--tosylpyrrolidines by means of an in situ (3 + 2) cycloaddition of the initially generated 2-aryl--tosylaziridine with residual styrene. In the presence of ketone, 1,3-oxazolidines can be formed in practicable yields, involving a single-pot cycloaddition reaction of alkene, nitrene, and ketone (2 + 1 + 2). Mechanistic studies indicate that the most productive bipodal Fe(II) site mediates stepwise addition of nitrene to olefins to generate aziridines with good retention of stereochemistry and further enables aziridine ring opening to unmask a 1,3-zwitterion that can undergo cycloaddition with dipolarophiles (MeCN, alkene, ketone) to afford five-membered -heterocycles.
PubMed: 37352838
DOI: 10.1021/acs.inorgchem.3c01209