Macrocyclic Imines Research Articles

Vibrational and electronic circular dichroism monitoring of copper(II) coordination with a chiral ligand

Novel copper(II) coordination compounds with chiral macrocyclic imine ligands derived from R-/S-camphor were asymmetrically synthesized and characterized with the aid of chiroptical spectroscopies. Crystal structures of both enantiomers were determined by single crystal X-ray diffraction analysis. Circular dichroism (CD) spectra were analyzed using a simplified exciton model as well as quantum chemical computations. The absolute configuration of the copper(II) coordination compounds determined from CD was found consistent with the crystal data. The copper(II) complexes were further investigated by vibrational CD (VCD) measurement combined with density functional theory calculation. The complex formation was evidenced by spectral shifts of the characteristic bands in the CD and VCD spectra.

Comparative Genomic and Transcriptomic Characterization of the Toxigenic Marine Dinoflagellate Alexandrium ostenfeldii

Many dinoflagellate species are notorious for the toxins they produce and ecological and human health consequences associated with harmful algal blooms (HABs). Dinoflagellates are particularly refractory to genomic analysis due to the enormous genome size, lack of knowledge about their DNA composition and structure, and peculiarities of gene regulation, such as spliced leader (SL) trans-splicing and mRNA transposition mechanisms. Alexandrium ostenfeldii is known to produce macrocyclic imine toxins, described as spirolides. We characterized the genome of A. ostenfeldii using a combination of transcriptomic data and random genomic clones for comparison with other dinoflagellates, particularly Alexandrium species. Examination of SL sequences revealed similar features as in other dinoflagellates, including Alexandrium species. SL sequences in decay indicate frequent retro-transposition of mRNA species. This probably contributes to overall genome complexity by generating additional gene copies. Sequencing of several thousand fosmid and bacterial artificial chromosome (BAC) ends yielded a wealth of simple repeats and tandemly repeated longer sequence stretches which we estimated to comprise more than half of the whole genome. Surprisingly, the repeats comprise a very limited set of 79–97 bp sequences; in part the genome is thus a relatively uniform sequence space interrupted by coding sequences. Our genomic sequence survey (GSS) represents the largest genomic data set of a dinoflagellate to date. Alexandrium ostenfeldii is a typical dinoflagellate with respect to its transcriptome and mRNA transposition but demonstrates Alexandrium-like stop codon usage. The large portion of repetitive sequences and the organization within the genome is in agreement with several other studies on dinoflagellates using different approaches. It remains to be determined whether this unusual composition is directly correlated to the exceptionally genome organization of dinoflagellates with a low amount of histones and histone-like proteins.

Synthesis of Cyclophanes with Planar and Helical Chirality

Novel helical macrocyclic imines derived from planar chiral [2.2]paracyclophane were synthesized. The chiroptical properties of the enantiopure compounds were investigated and their absolute configurations were assigned.

ChemInform Abstract: Facile Synthesis of Some New Macrocyclic Imine Ligands from Dehydroacetic Acid.

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Four Novel 30-Membered Imine and Amine Macrocycles Derived from Ortho-Aminophenyl Diamines

Two novel macrocyclic tetra-imine-diphenol Schiff base (H2L1 and H2L2) were synthesized by [2 + 2] cyclocondensation of ortho-aminophenyl diamines [1,2-bis(2′-aminophenoxy)benzene (I) and 1,2-bis(2′-aminophenoxy)-4-t-butylbenzene (II)] with 2,6-diformyl-4-methylphenol. Two novel tetra-amine-diphenol macrocycles (H2L3 and H2L4) have been obtained by reduction of the imine analogs with NaBH4 in MeOH/CHCl3.

Evolution of a Constitutional Dynamic Library Driven by Self-Organisation of a Helically Folded Molecular Strand

Conversion of macrocyclic imine entities into helical strands was achieved through three- and four-component exchange reactions within constitutionally dynamic libraries. The generation of sequences of the intrinsic helicity codon, based on the hydrazone-pyrimidine fragment obtained by condensation of pyrimidine dialdehyde A with pyrimidine bis-hydrazine B, shifted the equilibrium between all the possible macrocycles and strands towards the full expression (>98%) of helical product [A/B]. Furthermore, it was shown that chain folding accelerated the dynamic exchange reactions among the library members. Lastly, in four-component experiments (involving A, B, E and either C or D), even though the macrocyclic entities ([A/C], [B/E]; [A/D], [B/E]) were the kinetically preferred products, over time dialdehyde A relinquished its initial diamine partners C or D to opt for bis-hydrazine B, which allowed the preferential formation of the helically folded strand. The present results indicate that self-organisation pressure was able to drive the dynamic system towards the selective generation of the strand undergoing helical folding.

Structural determinants in phycotoxins and AChBP conferring high affinity binding and nicotinic AChR antagonism

Spirolide and gymnodimine macrocyclic imine phycotoxins belong to an emerging class of chemical agents associated with marine algal blooms and shellfish toxicity. Analysis of 13-desmethyl spirolide C and gymnodimine A by binding and voltage-clamp recordings on muscle-type alpha1(2)betagammadelta and neuronal alpha3beta2 and alpha4beta2 nicotinic acetylcholine receptors reveals subnanomolar affinities, potent antagonism, and limited subtype selectivity. Their binding to acetylcholine-binding proteins (AChBP), as soluble receptor surrogates, exhibits picomolar affinities governed by diffusion-limited association and slow dissociation, accounting for apparent irreversibility. Crystal structures of the phycotoxins bound to Aplysia-AChBP ( approximately 2.4A) show toxins neatly imbedded within the nest of ar-omatic side chains contributed by loops C and F on opposing faces of the subunit interface, and which in physiological conditions accommodates acetylcholine. The structures also point to three major features: (i) the sequence-conserved loop C envelops the bound toxins to maximize surface complementarity; (ii) hydrogen bonding of the protonated imine nitrogen in the toxins with the carbonyl oxygen of loop C Trp147 tethers the toxin core centered within the pocket; and (iii) the spirolide bis-spiroacetal or gymnodimine tetrahydrofuran and their common cyclohexene-butyrolactone further anchor the toxins in apical and membrane directions, along the subunit interface. In contrast, the se-quence-variable loop F only sparingly contributes contact points to preserve the broad receptor subtype recognition unique to phycotoxins compared with other nicotinic antagonists. These data offer unique means for detecting spiroimine toxins in shellfish and identify distinctive ligands, functional determinants and binding regions for the design of new drugs able to target several receptor subtypes with high affinity.

Triphenylamine-based rhombimine macrocycles with solution interconvertable conformation

Three imine macrocycles having rhomboidal shape were synthesized in good yields by [2+2] cyclocondensation reaction between equimolar quantities of (R,R)-1,2-diaminocyclohexane and 4,4'-bisformyl triphenylamine derivatives. The macrocycles structure was assigned by electrospray ionization mass spectrometry (ESI-MS), (1)H-NMR, and elemental analysis. UV, FTIR spectroscopy, and TG measurements were also used to characterize and prove the structure of these compounds. A conformational modification arising out of the rotation of triphenylamine group around the flexible cyclohexane-N bonds was observed in solution by (1)H-NMR and UV spectroscopy for all three macrocycles.

Synthesis, structure and chiroptical study of chiral macrocyclic imine nickel(ii) coordination compounds derived from camphor

A couple of enantiomers of novel chiral macrocyclic imines based on R/S-camphor were asymmetrically synthesized. Through the chiral macrocyclic ligands, enantiomers of nickel(II) coordination compounds were obtained. The chirality of the ligand was transferred to the nickel atom upon coordination, leading to predetermined configuration. The chiral ligands and corresponding nickel coordination compounds were characterized by UV, IR, CD, VCD spectra and single crystal X-ray crystallography. The structural and spectroscopic properties were further investigated by DFT calculations.

Synthesis and Characterization of Novel 30-Membered Imine and Amine Macrocycles Derived from ortho-Aminophenyl Diamines and 2,6-Diformyl-4-chlorophenol

Two novel macrocyclic tetraimine-diphenol Schiff bases were synthesized by [2+2] cyclocondensation of ortho-aminophenyl diamines [1,2-bis(2'-aminophenoxy)benzene and 1,2-bis(2'-aminophenoxy)-4-tert-butylbenzene] with 2,6-diformyl-4-chlorophenol (dcp). Two novel tetraamine-diphenol macrocycles were obtained by reduction of the imine analogues with sodium borohydride in methanol/chloroform.

A Facile One-Pot Three-Component Synthesis of Macrocyclic Imidazolidines by [3+2] Cycloaddition Reaction of Azomethine Ylides

One-pot three-component synthesis of novel macrocyclic imidazolidines has been accomplished in good yields via a facile [3+2] cycloaddition reaction of azomethine ylide, derived from paraformaldehyde and sarcosine, with various macrocyclic imines as dipolarophiles. The effect of solvent on the [3+2]-dipolar cycloaddition reaction is also studied.

Arylene Imine Macrocycles of C3h and C3 Symmetry from Reductive Imination of Nitroformylarenes

Novel C(3)-symmetric phenylene imine macrocycles have been synthesized by reductive imination of single nitroformylarenes. Pore size and geometric shape are dictated by the distance between and orientation of the nitro and aldehyde moieties in the precursor backbone. This reaction is facile, requires no purification of the products, and is environmentally friendly.

HIGH PROBABILITY OF LARGE ORBITAL ANGULAR MOMENTUM CONTRIBUTION TO THE MAGNETIC MOMENT OF COBALT(II) ION IN NEWLY REPORTED MACROCYCLIC COMPLEX CONTAINING AMIDE, IMINE AND SECONDARY AMINE FUNCTIONS

Article HIGH PROBABILITY OF LARGE ORBITAL ANGULAR MOMENTUM CONTRIBUTION TO THE MAGNETIC MOMENT OF COBALT(II) ION IN NEWLY REPORTED MACROCYCLIC COMPLEX CONTAINING AMIDE, IMINE AND SECONDARY AMINE FUNCTIONS was published on July 1, 2008 in the journal Reviews in Inorganic Chemistry (volume 28, issue 3).

Atom transfer radical polymerization of some vinyl monomers catalyzed by imine macrocycle copper (I) complex

Imine macrocyclic ligand (M1) was used in conjunction with CuBr as novel catalytic system in atom transfer radical polymerization (ATRP) of methylmethacrylate (MMA), butylmethacrylate (n-BuMA) and 2- dimethylaminoethylmethacrylate (DMAEMA). Two different initiators were involved such as Br-methoxypolyoxyethylene macroinitiator and 1, 3, 5-(2-bromo-2‘-methylpropionato) benzene three arm star initiator. The polymerization reactions were conducted at 90 °C in toluene. The macrocyclic ligand M1 demonstrated peculiar behavior which was monitored by the GPC measurements whether with respect to the polydispersities or the molar masses. High molar masses than expected were obtained except incase of DMAEMA monomer. The structures of the formed polymers were proven via 1HNMR.

On the allelochemical potency of the marine dinoflagellate Alexandrium ostenfeldii against heterotrophic and autotrophic protists

Three strains of the marine dinoflagellate Alexandrium ostenfeldii of different geographic origin were tested for their short-term deleterious effects on a diversity of marine protists. All A. ostenfeldii strains were capable of eliciting an apparent allelochemical response, but the various protistan target species were differentially affected. Protists that were negatively affected by exposure to cells of A. ostenfeldii and associated extracellular metabolites comprised both autotrophs (Rhodomonas sp., Dunaliella salina, Thalassiosira weissflogii) and heterotrophs (Oxyrrhis marina, Amphidinium crassum, Rimostrombidium caudatum). Observed effects included immobilisation (e.g. of O. marina), morphological changes (e.g. in D. salina) and/or aberrant behaviour (e.g. of R. caudatum), mainly as preliminary stages of cell lysis. Immobilization and lytic effects against O. marina were strongly dependent on A. ostenfeldii cell concentrations. Effects also differed substantially among strains and different batch cultures of the same strain. Values of EC50, defined as the A. ostenfeldii cell concentration causing lysis of 50% of O. marina cells, ranged from 0.3 to 1.9 � 10 3 mL 21 , depending on the A. ostenfeldii strain. The autotrophic dinoflagellate Scrippsiella trochoidea reacted to exposure to A. ostenfeldii cells by formation of temporary (ecdysal) cysts, whereas, in contrast, the flagellates Emiliania huxleyi and Prymnesium parvum and the ciliate Strombidium sp. were relatively refractory or even unaffected. As long as cells did not lyse, the fluorescence yield of target autotrophs, estimated by pulse-amplitude modulation fluorometry, did not significantly change during the first 3 h of incubation, suggesting that allelochemicals produced by A. ostenfeldii caused no shortterm negative effects on the photosynthetic apparatus. Overall, the allelochemical responses of target species showed no obvious relationship to cell quota or extracellular concentrations of either toxic macrocyclic imines (spirolides) or tetrahydropurine neurotoxins (saxitoxin and analogues) produced by various strains of A. ostenfeldii. Instead, the potency of A. ostenfeldii, eliciting immobilization and lytic species-specific responses in potential predators and competitors, is consistent with the existence of an allelochemical mechanism unrelated to the bioactivity of known phycotoxins of the genus Alexandrium.

Peptide Macrocyclization: The Reductase of the Nostocyclopeptide Synthetase Triggers the Self-Assembly of a Macrocyclic Imine

Many biologically active natural products have macrocyclic structures. In nonribosomal peptides macrocyclization is commonly achieved via the formation of intramolecular ester or amide bond catalyzed by thioesterase domains during biosynthesis. A unique and so far unknown type of peptide cyclization occurs in the nostocyclopeptide, a macrocyclic imine produced by the terrestrial cyanobacterium Nostoc sp. ATCC53789. In this work we show that a C-terminal reductase domain of the nostocyclopeptide nonribosomal peptide synthetase catalyzes the reductive release of a linear peptide aldehyde and thereby triggers the spontaneous formation of a stable imino head-to-tail linkage. This type of molecular self-assembly induced by the reductive release of reactive aldehydes may be more commonplace in other complex nonribosomal peptides than originally thought.

Preparation and Characterization of Homo‐ and Co‐Polymers of Some Vinyl Monomers via ATRP by Using Imine Macrocycle as Ligand

Imine macrocyclic ligand M1 was involved in homo‐ and co‐polymerization of some vinyl monomers via atom transfer radical polymerization technique (ATRP). Hereby, vinyl acetate, styrene and methyl acrylate monomers were homopolymerized. On the other hand, they were involved in copolymerization with MMA. M1∶CuBr∶initiator∶monomer percentages were 1∶2∶4∶400. 1HNMR confirmed the structures of the resulting polymers. The thermal behaviors of some selected polymers were studied.

Microwave‐Assisted Cyclocondensation of Dialdehydes with Chiral Diamines Forming Calixsalen Type Macrocycles.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Employing Imine Macrocycle Ligand in the Atom Transfer Radical Polymerization of Methyl Methacrylate

Imine macrocycle M1 was successfully used in conjunction with CuBr as a catalytic system in the atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA). The role of the reaction conditions was clearly observed. Such reaction conditions were found to be the molar ratios of the reactants, the chosen initiating systems, and some additional ambient conditions (e.g. temperature, solvent). MMA homopolymers were successively prepared via ATRP by using benzhydrylbromide, diethylmethylbromomalonate initiating systems under the appropriate reaction conditions. Definite well‐known structures of the formed polymers were unambiguously identified with 1H NMR.

Microwave assisted cyclocondensation of dialdehydes with chiral diamines forming calixsalen type macrocycles

Microwave irradiation of various dialdehydes and chiral diamines afforded chiral macrocyclic imines in moderate to good yields. Linked dialdehydes predominantly form [2+2] macrocycles whereas dialdehydes without linkers yield [3+3] macrocycles. This is the first report of template-free synthesis of calixsalen-type macrocycles formed in shorter reaction times under microwave conditions. In all the reactions, the salts of chiral diamines were used in contrast to the free diamines normally employed.