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Inorganic Chemistry Aug 2023Diamine ligands are effective structural scaffolds for tuning the reactivity of transition-metal complexes for catalytic, materials, and phosphorescent applications and...
Diamine ligands are effective structural scaffolds for tuning the reactivity of transition-metal complexes for catalytic, materials, and phosphorescent applications and have been leveraged for biological use. In this work, we report the synthesis and characterization of a novel class of cyclometalated [C^N] Au(III) complexes bearing secondary diamines including a norbornane backbone, (2,3)-,-dibenzylbicyclo[2.2.1]heptane-2,3-diamine, or a cyclohexane backbone, (1,2)-,-dibenzylcyclohexane-1,2-diamine. X-ray crystallography confirms the square-planar geometry and chirality at nitrogen. The electronic character of the conformationally restricted norbornane backbone influences the electrochemical behavior with redox potentials of -0.8 to -1.1 V, atypical for Au(III) complexes. These compounds demonstrate promising anticancer activity, particularly, complex , which bears a benzylpyridine organogold framework, and supported by the bicyclic conformationally restricted diaminonorbornane, shows good potency in A2780 cells. We further show that a cellular response to evokes reactive oxygen species (ROS) production and does not induce mitochondrial dysfunction. This class of complexes provides significant stability and reactivity for different applications in protein modification, catalysis, and therapeutics.
Topics: Female; Humans; Gold; Antineoplastic Agents; Cell Line, Tumor; Ovarian Neoplasms; Crystallography, X-Ray; Diamines; Norbornanes; Ligands
PubMed: 37530672
DOI: 10.1021/acs.inorgchem.3c02066 -
Chinese Medical Journal Jan 2019Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the cornerstone of treatment in patients with acute coronary syndromes (ACS) and in those... (Review)
Review
OBJECTIVE
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the cornerstone of treatment in patients with acute coronary syndromes (ACS) and in those undergoing percutaneous coronary intervention (PCI). In current clinical situation, availability of different oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor) has enabled physicians to switch among therapies owing to specific clinical scenarios. Although optimum time, loading dose and interval of transition between P2Y12 inhibitors is still controversial and needs further evidence, switching between oral inhibitors frequently occurs in clinical practice for several reasons.
DATA SOURCES
This review was based on data in articles published in PubMed up to June 2018, with the following keywords "antiplatelet therapy", "ACS", "PCI", "ticagrelor", and "clopidogrel".
STUDY SELECTION
Original articles and critical reviews on de-escalation strategy in ACS patients after PCI were selected. References of the retrieved articles were also screened to search for potentially relevant papers.
RESULTS
Safety concerns associated with switching between antiplatelet agents, has prompted the use of clopidogrel for patients with ACS especially after PCI as a de-escalation strategy. Practical considerations for de-escalating therapies in patients with ACS such as reducing dose of P2Y12 inhibitors or shortening duration of DAPT (followed by aspirin or P2Y12 receptor inhibitor monotherapy) as potential options are yet to be standardized and validated.
CONCLUSIONS
Current review will provide an overview of the pharmacology of common P2Y12 inhibitors, definitions of de-escalation and different de-escalating strategies and its outcomes, along with possible direction to be explored in de-escalation.
Topics: Acute Coronary Syndrome; Aspirin; Diamines; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Thiazoles
PubMed: 30614864
DOI: 10.1097/CM9.0000000000000047 -
Journal of the American Chemical Society Dec 2018The widespread deployment of carbon capture and sequestration as a climate change mitigation strategy could be facilitated by the development of more energy-efficient...
The widespread deployment of carbon capture and sequestration as a climate change mitigation strategy could be facilitated by the development of more energy-efficient adsorbents. Diamine-appended metal-organic frameworks of the type diamine-M(dobpdc) (M = Mg, Mn, Fe, Co, Ni, Zn; dobpdc = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) have shown promise for carbon-capture applications, although questions remain regarding the molecular mechanisms of CO uptake in these materials. Here we leverage the crystallinity and tunability of this class of frameworks to perform a comprehensive study of CO chemisorption. Using multinuclear nuclear magnetic resonance (NMR) spectroscopy experiments and van-der-Waals-corrected density functional theory (DFT) calculations for 13 diamine-M(dobpdc) variants, we demonstrate that the canonical CO chemisorption products, ammonium carbamate chains and carbamic acid pairs, can be readily distinguished and that ammonium carbamate chain formation dominates for diamine-Mg(dobpdc) materials. In addition, we elucidate a new chemisorption mechanism in the material dmpn-Mg(dobpdc) (dmpn = 2,2-dimethyl-1,3-diaminopropane), which involves the formation of a 1:1 mixture of ammonium carbamate and carbamic acid and accounts for the unusual adsorption properties of this material. Finally, we show that the presence of water plays an important role in directing the mechanisms for CO uptake in diamine-M(dobpdc) materials. Overall, our combined NMR and DFT approach enables a thorough depiction and understanding of CO adsorption within diamine-M(dobpdc) compounds, which may aid similar studies in other amine-functionalized adsorbents in the future.
Topics: Adsorption; Carbamates; Carbon Dioxide; Density Functional Theory; Diamines; Metal-Organic Frameworks; Models, Chemical; Temperature; Water
PubMed: 30501180
DOI: 10.1021/jacs.8b10203 -
Macromolecular Rapid Communications Feb 2019The synthesis of macrocycles based on the Ugi-4CR has been thoroughly explored by Wessjohann and coworkers, while polymerizations utilizing the Ugi-4CR are already...
The synthesis of macrocycles based on the Ugi-4CR has been thoroughly explored by Wessjohann and coworkers, while polymerizations utilizing the Ugi-4CR are already patented by Ugi and recently studied more in detail, developing a new trend in polymer chemistry. Here, the combination of both, that is, the synthesis of polymacrocycles, is demonstrated. As diverse functional groups can be easily introduced in a macrocycle via Ugi-4CR, a straightforward design of polymacrocycles is achieved in a two-step procedure. First, the Ugi-4CR of 10-undecenoic acid, a diamine, a diisocyanide, and an aldehyde results in diversely substituted macrocycles having two terminal double bonds. Subsequently, these macrocycles are polymerized by ADMET (acyclic diene metathesis) or thiol-ene polymerization to generate polymacrocycles with potential application in coordination chemistry as, for example, sensors, filters, or phase-transfer catalysts. Moreover, the setup of the literature-known Ugi macrocyclization is simplified by systematic reaction screening.
Topics: Aldehydes; Cyanides; Cyclization; Diamines; Macrocyclic Compounds; Molecular Structure; Polymerization; Polymers; Undecylenic Acids
PubMed: 30457196
DOI: 10.1002/marc.201800748 -
European Journal of Medicinal Chemistry Jan 2022Inhibition of mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1) is a promising strategy to modulate NF-κB signaling, with the potential to...
Inhibition of mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1) is a promising strategy to modulate NF-κB signaling, with the potential to treat B-cell lymphoma and autoimmune diseases. We describe the discovery and optimization of (1s,4s)-N,N'-diaryl cyclohexane-1,4-diamines, a novel series of allosteric MALT1 inhibitors, resulting in compound 8 with single digit micromolar cell potency. X-ray analysis confirms that this compound binds to an induced allosteric site in MALT1. Compound 8 is highly selective and has an excellent in vivo rat PK profile with low clearance and high oral bioavailability, making it a promising lead for further optimization.
Topics: Allosteric Regulation; Animals; Cyclohexanes; Diamines; Dose-Response Relationship, Drug; Drug Discovery; Humans; Molecular Structure; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; Rats; Structure-Activity Relationship
PubMed: 34742013
DOI: 10.1016/j.ejmech.2021.113925 -
Journal of Agricultural and Food... Jul 2023Severe plant virus diseases lead to poor harvests and poor crop quality, and the lack of effective suppressive drugs makes plant disease control a huge challenge....
Severe plant virus diseases lead to poor harvests and poor crop quality, and the lack of effective suppressive drugs makes plant disease control a huge challenge. Natural product-based structural simplification is an important strategy for finding novel pesticide candidates. According to our previous research on the antiviral activities of harmine and tetrahydroharmine derivatives, a series of chiral diamine compounds were designed and synthesized by means of structural simplification using diamines in natural products as the core structure in this work, and the antiviral and fungicidal activities were investigated. Most of these compounds displayed higher antiviral activities than those of ribavirin. Compounds and displayed higher antiviral activities than ningnanmycin at 500 μg/mL. The antiviral mechanism research revealed that compounds and could inhibit virus assembly by binding to tobacco mosaic virus (TMV) CP and interfere with the assembly process of TMV CP and RNA transmission electron microscopy and molecular docking. Further fungicidal activity tests showed that these compounds displayed broad-spectrum fungicidal activities. Compounds , , , and with excellent fungicidal activities against f.sp. can be considered as new fungicidal candidates for further research. The current work provides a reference to the development of agricultural active ingredients in crop protection.
Topics: Antiviral Agents; Structure-Activity Relationship; Diamines; Molecular Docking Simulation; Fungicides, Industrial; Tobacco Mosaic Virus; Biological Products; Drug Design
PubMed: 37433073
DOI: 10.1021/acs.jafc.3c01247 -
The Journal of Organic Chemistry Jun 2023Chiral Ni complexes have revolutionized both asymmetric acid-base and redox catalysis. However, the coordination isomerism of Ni complexes and their open-shell property...
Chiral Ni complexes have revolutionized both asymmetric acid-base and redox catalysis. However, the coordination isomerism of Ni complexes and their open-shell property still often hinder the elucidation of the origin of their observed stereoselectivity. Here, we report our experimental and computational investigations to clarify the mechanism of β-nitrostyrene facial selectivity switching in Ni(II)-diamine-(OAc)-catalyzed asymmetric Michael reactions. In the reaction with a dimethyl malonate, the Evans transition state (TS), in which the enolate binds in the same plane with the diamine ligand, is identified as the lowest-energy TS to promote C-C bond formation from the face in β-nitrostyrene. In contrast, a detailed survey of the multiple potential pathways in the reaction with α-keto esters points to a clear preference for our proposed C-C bond-forming TS, in which the enolate coordinates to the Ni(II) center in apical-equatorial positions relative to the diamine ligand, thereby promoting face addition in β-nitrostyrene. The N-H group plays a key orientational role in minimizing steric repulsion.
Topics: Nickel; Diamines; Ligands; Carboxylic Acids; Catalysis
PubMed: 36813263
DOI: 10.1021/acs.joc.2c02732 -
Journal of Environmental Sciences... Oct 2023In the present work, functional diamine groups into indium frameworks to synthesize cyclic carbonates from CO and epoxides with efficient catalytic activity in the...
In the present work, functional diamine groups into indium frameworks to synthesize cyclic carbonates from CO and epoxides with efficient catalytic activity in the absence of co-catalyst and solvent are reported for the first time. Crystalline porous materials (CPM)-5 modified with 1,2-phenylene diamine and ethylene diamine (CPM-5-PhDA and CPM-5-EDA), were prepared using a post-synthetic modification (PSM) method. The properties of the modified CPM-5 were characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), N-adsorption, scanning electron microscopy (SEM), CO adsorption, and temperature programmed desorption TPD methods. The presence of diamine groups as basic sites and indium Lewis acid sites in the framework structure were desirable for high catalytic activity. For a given catalyst weight, CPM-5-PhDA was the best candidate to appear with great catalytic activity and selectivity for the cycloaddition reaction at 100°C and 1 MPa CO under co-catalyst and solvent free conditions. CPM-5-PhDA also was found to afford large and bulky epoxides. The catalyst can be easily separated and reused five times without any decline in activity.
Topics: Indium; Solvents; Carbon Dioxide; Diamines; Porosity; Spectroscopy, Fourier Transform Infrared; Epoxy Compounds
PubMed: 37336602
DOI: 10.1016/j.jes.2022.08.029 -
Natural Product Reports Mar 2020Covering: 2006 to 2019Macrocyclic diamine alkaloids derived from 3-alkyldihydropyridine dimers comprise a diverse and highly complex family of natural products. The... (Review)
Review
Covering: 2006 to 2019Macrocyclic diamine alkaloids derived from 3-alkyldihydropyridine dimers comprise a diverse and highly complex family of natural products. The macrocyclic and caged structural features of these alkaloids have inspired many creative solutions from the synthetic organic community over the past 30 years. This review will cover the successful synthetic campaigns over the past decade, with a focus on (1) key bond disconnections and advances and (2) remaining challenges and opportunities for innovation within this natural product class.
Topics: Alkaloids; Biological Products; Bridged-Ring Compounds; Carbazoles; Carbolines; Diamines; Heterocyclic Compounds, 4 or More Rings; Macrocyclic Compounds; Piperidines; Quinolizidines; Quinolizines; Spiro Compounds
PubMed: 31524907
DOI: 10.1039/c9np00031c -
Biomolecules Jul 2021Allograft kidney transplantation, which triggers host cellular- and antibody-mediated rejection of the kidney, is a major contributor to kidney damage during transplant....
Allograft kidney transplantation, which triggers host cellular- and antibody-mediated rejection of the kidney, is a major contributor to kidney damage during transplant. Here, we asked whether PrC-210 would suppress damage seen in allograft kidney transplant. Brown Norway (BN) rat kidneys were perfused in situ (UW Solution) with or without added 30 mM PrC-210, and then immediately transplanted into Lewis (LEW) rats. 20 h later, the transplanted BN kidneys and LEW rat plasma were analyzed. Kidney histology, and kidney/serum levels of several inflammation-associated cytokines, were measured to assess mismatch-related kidney pathology, and PrC-210 protective efficacy. Twenty hours after the allograft transplants: (i) significant histologic kidney tubule damage and mononuclear inflammatory cell infiltration were seen in allograft kidneys; (ii) kidney function metrics (creatinine and BUN) were significantly elevated; (iii) significant changes in key cytokines, i.e., TIMP-1, TNF-alpha and MIP-3A/CCL20, and kidney activated caspase levels were seen. In PrC-210-treated kidneys and recipient rats, (i) kidney histologic damage (Banff Scores) and mononuclear infiltration were reduced to untreated background levels; (ii) creatinine and BUN were significantly reduced; and (iii) activated caspase and cytokine changes were significantly reduced, some to background. In conclusion, the results suggest that PrC-210 could provide broadly applicable organ protection for many allograft transplantation conditions; it could protect transplanted kidneys during and after all stages of the transplantation process-from organ donation, through transportation, re-implantation and the post-operative inflammation-to minimize acute and chronic rejection.
Topics: Adenosine; Allografts; Allopurinol; Animals; Caspases; Creatinine; Cytokines; Diamines; Free Radical Scavengers; Glutathione; Inflammation; Insulin; Kidney; Kidney Transplantation; Male; Mitochondria; Organ Preservation Solutions; Raffinose; Rats, Inbred BN; Rats, Inbred Lew; Sulfhydryl Compounds; Rats
PubMed: 34356678
DOI: 10.3390/biom11071054