-
Veterinary Parasitology Aug 2021Gastrointestinal nematodes (GIN) infections are a serious problem in livestock production due to the great economic losses they cause. Their control is increasingly...
Gastrointestinal nematodes (GIN) infections are a serious problem in livestock production due to the great economic losses they cause. Their control is increasingly difficult because of the rapid development of drug resistance and the limited number of available drugs. Therefore, this study evaluated 18 aminoalcohol and 16 diamine derivatives against eggs, first and third stage larvae from a susceptible and a resistant isolate of Teladorsagia circumcincta collected from sheep. The effectiveness of the in vitro anthelmintic activity of the compounds was evaluated using three different procedures: Egg Hatch Test (EHT), Larval Mortality Test (LMT) and Larval Migration Inhibition Test (LMIT). Those compounds with activities higher than 90 % in the initial screening at 50 μM were selected to determine their half maximal effective concentration (EC). In parallel, cytotoxicity assays were conducted on Caco2 and HepG2 cell lines to calculate Selectivity Indexes (SI) for each compound. The diamine 30 presented the best results in preventing egg hatching, displaying the lowest EC value (1.01 ± 0.04 μM) of all compounds tested and the highest SI (21.21 vs. Caco-2 cells). For the LMIT, the diamine 34 showed the highest efficacy, with EC values of 2.67 ± 0.08 and 3.02 ± 0.09 μM on the susceptible and resistant isolate of the parasite, respectively.
Topics: Alcohols; Animals; Anthelmintics; Caco-2 Cells; Diamines; Drug Resistance; Feces; Humans; Nematoda; Ovum; Sheep; Sheep Diseases
PubMed: 34147018
DOI: 10.1016/j.vetpar.2021.109496 -
Topics in Current Chemistry (Cham) Aug 2017Developments and progress in polymer science are often inspired by organic chemistry. In recent years, multicomponent reactions-especially the Passerini and Ugi... (Review)
Review
Developments and progress in polymer science are often inspired by organic chemistry. In recent years, multicomponent reactions-especially the Passerini and Ugi reactions-have become very important tools for macromolecular design, mainly due to their modular character. In this review, the versatility of the Passerini and Ugi reactions in polymer science is highlighted by discussing recent examples of their use for monomer synthesis, as polymerization techniques, and for postpolymerization modification, as well as their suitability for architecture control, sequence control, and sequence definition.
Topics: Acrylates; Catalysis; Cyanides; Diamines; Metals; Polymerization; Polymers
PubMed: 28608298
DOI: 10.1007/s41061-017-0153-4 -
Nature Protocols Dec 2021Fluorine is a key element present in ~35% of agrochemicals and 25% of marketed pharmaceutical drugs. The availability of reliable synthetic protocols to prepare... (Review)
Review
Fluorine is a key element present in ~35% of agrochemicals and 25% of marketed pharmaceutical drugs. The availability of reliable synthetic protocols to prepare catalysts that allow the efficient incorporation of fluorine in organic molecules is therefore essential for broad applicability. Herein, we report a protocol for the multigram synthesis of two representative enantiopure N-alkyl bis-urea organocatalysts derived from (S)-(-)-1,1'-binaphthyl-2,2'-diamine ((S)-BINAM). These tridentate hydrogen bond donors are highly effective phase-transfer catalysts for solubilizing safe and inexpensive metal alkali fluorides (KF and CsF) in organic solvents for enantioselective nucleophilic fluorinations. The first catalyst, characterized by N-isopropyl substitution, was obtained by using a two-step sequence consisting of reductive amination followed by urea coupling from commercially available starting materials (14 g, 48% yield and 5-d total synthesis time). The second catalyst, featuring N-ethyl alkylation and meta-terphenyl substituents, was accessed via a novel, scalable, convergent route that concluded with the coupling between N-ethylated (S)-BINAM and a preformed isocyanate (52 g and 52% overall yield). On this scale, the synthesis requires ~10 d. This can be reduced to 5 d by performing some steps in parallel. Compared to the previous synthetic route, this protocol avoids the final chromatographic purification and produces the desired catalysts in very high purity and improved yield.
Topics: Alkylation; Amination; Catalysis; Chemistry Techniques, Synthetic; Diamines; Fluorides; Fluorine; Halogenation; Humans; Hydrogen Bonding; Isocyanates; Naphthalenes; Oxidation-Reduction; Stereoisomerism; Terphenyl Compounds; Urea
PubMed: 34759385
DOI: 10.1038/s41596-021-00625-y -
Organic Letters Feb 2021A cobalt-catalyzed method for the C(sp)-C(sp) Suzuki-Miyaura cross coupling of aryl boronic esters and alkyl bromides is described. Cobalt-ligand combinations were...
A cobalt-catalyzed method for the C(sp)-C(sp) Suzuki-Miyaura cross coupling of aryl boronic esters and alkyl bromides is described. Cobalt-ligand combinations were assayed with high-throughput experimentation, and cobalt(II) sources with -,'-dimethylcyclohexane-1,2-diamine (DMCyDA, L) produced optimal yield and selectivity. The scope of this transformation encompassed steric and electronic diversity on the aryl boronate nucleophile as well as various levels of branching and synthetically valuable functionality on the electrophile. Radical trap experiments support the formation of electrophile-derived radicals during catalysis.
Topics: Bromides; Catalysis; Cobalt; Diamines; Esters; Ligands; Molecular Structure
PubMed: 32996312
DOI: 10.1021/acs.orglett.0c02934 -
Journal of the American Chemical Society Dec 2019The enantioselective, vicinal diamination of alkenes represents one of the stereocontrolled additions that remains an outstanding challenge in organic synthesis. A...
The enantioselective, vicinal diamination of alkenes represents one of the stereocontrolled additions that remains an outstanding challenge in organic synthesis. A general solution to this problem would enable the efficient and selective preparation of widely useful, enantioenriched diamines for applications in medicinal chemistry and catalysis. In this article, we describe the first enantioselective, diamination of simple alkenes mediated by a chiral, enantioenriched organoselenium catalyst together with a bistosyl urea as the bifunctional nucleophile and fluorocollidinium tetrafluoroborate as the stoichiometric oxidant. Diaryl, aryl-alkyl, and alkyl-alkyl olefins bearing a variety of substituents are all diaminated in consistently high enantioselectivities but variable yields. The reaction likely proceeds through a Se(II)/Se(IV) redox catalytic cycle reminiscent of the dichlorination reported previously. Furthermore, the -stereospecificity of the transformation shows promise for highly enantioselective diaminations of alkenes with no strong steric or electronic bias.
Topics: Alkenes; Amination; Catalysis; Diamines; Organoselenium Compounds; Oxidants; Oxidation-Reduction; Stereoisomerism; Urea
PubMed: 31742399
DOI: 10.1021/jacs.9b11261 -
Combinatorial Chemistry & High... 2018The transformation of low cost sugar feedstocks into market chemicals and monomers for existing or novel high performance polymers by chemical catalysis is reviewed.... (Review)
Review
The transformation of low cost sugar feedstocks into market chemicals and monomers for existing or novel high performance polymers by chemical catalysis is reviewed. Emphasis is given to industrially relevant, continuous flow, trickle bed processes. Since long-term catalyst stability under hydrothermal conditions is an important issue to be addressed in liquid phase catalysis using carbohydrate feedstocks, we will primarily discuss the results of catalytic performance for prolonged times on stream. In particular, the selective aerobic oxidation of glucose to glucaric acid and the subsequent selective hydrogenation to adipic acid is reviewed. Hydroxymethylfurfural (HMF), which is readily available from fructose, can be upgraded by oxidation to furan dicarboxylic acid (FDCA) or by consecutive reduction and hydrogenolysis to hexanetriol (HTO) followed by hydrogenolysis to biobased hexanediol (HDO). Direct amination of HDO yields biobased hexamethylene diamine (HMDA). Aerobic oxidation of HDO represents an alternative route to biobased adipic acid. HMDA and adipic acid are the monomers required for the production of nylon- 6,6, a major polymer for engineering and fibre applications.
Topics: Adipates; Catalysis; Chemical Industry; Diamines; Dicarboxylic Acids; Fructose; Furaldehyde; Furans; Glucaric Acid; Glucose; Oxidation-Reduction; Sugars; Xylose
PubMed: 30569863
DOI: 10.2174/1386207322666181219155050 -
Current Medicinal Chemistry 2020The discovery of cisplatin and the subsequent research revealed the importance of dinitrogen-containing moiety for the anticancer action of metal complexes. Moreover,...
BACKGROUND
The discovery of cisplatin and the subsequent research revealed the importance of dinitrogen-containing moiety for the anticancer action of metal complexes. Moreover, certain diamine ligands alone display cytotoxicity that contributes to the overall activity of corresponding complexes.
OBJECTIVE
To summarize the current knowledge on the anticancer efficacy, selectivity, and the mechanisms of action of metal complexes with various types of diamine ligands.
METHODS
The contribution of aliphatic acyclic, aliphatic cyclic, and aromatic diamine ligands to the anticancer activity and selectivity/toxicity of metal complexes with different metal ions were analyzed by comparison with organic ligand alone and/or conventional platinum-based chemotherapeutics.
RESULTS
The aliphatic acyclic diamine ligands are present mostly in complexes with platinum. Aliphatic cyclic diamines are part of Pt(II), Ru(II) and Au(III) complexes, while aromatic diamine ligands are found in Pt(II), Ru(II), Pd(II) and Ir(III) complexes. The type and oxidation state of metal ions greatly influences the cytotoxicity of metal complexes with aliphatic acyclic diamine ligands. Lipophilicity of organic ligands, dependent on alkyl-side chain length and structure, determines their cellular uptake, with edda and eddp/eddip ligands being most useful in this regard. Aliphatic cyclic diamine ligands improved the activity/toxicity ratio of oxaliplatin-type complexes. The complexes with aromatic diamine ligands remain unexplored regarding their anticancer mechanism. The investigated complexes mainly caused apoptotic or necrotic cell death.
CONCLUSION
Metal complexes with diamine ligands are promising candidates for efficient and more selective alternatives to conventional platinum-based chemotherapeutics. Further research is required to reveal the chemico-physical properties and molecular mechanisms underlying their biological activity.
Topics: Antineoplastic Agents; Cisplatin; Coordination Complexes; Diamines; Ligands
PubMed: 30378486
DOI: 10.2174/0929867325666181031114306 -
Journal of Biological Inorganic... Oct 2018Dihydroxamic acid macrocyclic siderophores comprise four members: putrebactin (putH), avaroferrin (avaH), bisucaberin (bisH), and alcaligin (alcH). This mini-review... (Review)
Review
Dihydroxamic acid macrocyclic siderophores comprise four members: putrebactin (putH), avaroferrin (avaH), bisucaberin (bisH), and alcaligin (alcH). This mini-review collates studies of the chemical biology and coordination chemistry of these macrocycles, with an emphasis on putH. These Fe(III)-binding macrocycles are produced by selected bacteria to acquire insoluble Fe(III) from the local environment. The macrocycles are optimally pre-configured for Fe(III) binding, as established from the X-ray crystal structure of dinuclear [Fe(alc)] at neutral pH. The dimeric macrocycles are biosynthetic products of two endo-hydroxamic acid ligands flanked by one amine group and one carboxylic acid group, which are assembled from 1,4-diaminobutane and/or 1,5-diaminopentane as initial substrates. The biosynthesis of alcH includes an additional diamine C-hydroxylation step. Knowledge of putH biosynthesis supported the use of precursor-directed biosynthesis to generate unsaturated putH analogues by culturing Shewanella putrefaciens in medium supplemented with unsaturated diamine substrates. The X-ray crystal structures of putH, avaH and alcH show differences in the relative orientations of the amide and hydroxamic acid functional groups that could prescribe differences in solvation and other biological properties. Functional differences have been borne out in biological studies. Although evolved for Fe(III) acquisition, solution coordination complexes have been characterised between putH and oxido-V(IV/V), Mo(VI), or Cr(V). Retrosynthetic analysis of 1:1 complexes of [Fe(put)], [Fe(ava)], and [Fe(bis)] that dominate at pH < 5 led to a forward metal-templated synthesis approach to generate the Fe(III)-loaded macrocycles, with apo-macrocycles furnished upon incubation with EDTA. This mini-review aims to capture the rich chemistry and chemical biology of these seemingly simple compounds.
Topics: Coordination Complexes; Ferric Compounds; Hydroxamic Acids; Molecular Structure; Peptides, Cyclic; Putrescine; Succinates
PubMed: 29946977
DOI: 10.1007/s00775-018-1585-1 -
Chemical Reviews Nov 2015
Review
Topics: Acetyltransferases; Azepines; Azo Compounds; Carbazoles; Diamines; Drug Evaluation, Preclinical; Humans; Protein Binding; Protein Structure, Tertiary; Quinolines; Small Molecule Libraries; Transcription Factors
PubMed: 26492937
DOI: 10.1021/acs.chemrev.5b00205 -
Physical Review Letters Feb 2021The interaction between proteins and hydration water stabilizes protein structure and promotes functional dynamics, with water translational motions enabling protein...
The interaction between proteins and hydration water stabilizes protein structure and promotes functional dynamics, with water translational motions enabling protein flexibility. Engineered solvent-free protein-polymer hybrids have been shown to preserve protein structure, function, and dynamics. Here, we used neutron scattering, protein and polymer perdeuteration, and molecular dynamics simulations to explore how a polymer dynamically replaces water. Even though relaxation rates and vibrational properties are strongly modified in polymer coated compared to hydrated proteins, liquidlike polymer dynamics appear to plasticize the conjugated protein in a qualitatively similar way as do hydration-water translational motions.
Topics: Diamines; Glycolates; Hydrogen Bonding; Molecular Dynamics Simulation; Myoglobin; Neutron Diffraction; Polyethylene Glycols; Polymers; Protein Conformation; Proteins; Thermodynamics; Water
PubMed: 33709739
DOI: 10.1103/PhysRevLett.126.088102