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Natural enediyne antibiotics undergo thermally induced cycloaromatization under physiological conditions to generate highly reactive diradicals that effectively abstract hydrogen atoms from biomacromolecules like DNA, leading to DNA cleavage and inducing programmed cell death in tumor cells, exhibiting potent cytotoxicity and broad‐spectrum antitumor properties. In order to further explore promising synthetic analogues of natural enediynes, a 3,6‐pyridazinedione moiety was fused at the ene‐position, and 10 new enediyne compounds with different atoms at the propargylic positions were synthesized. Differential scanning calorimetry (DSC) and electron paramagnetic resonance results indicated that these enediynes exhibited a rather low onset temperature and the capability to generate radical species at physiological temperatures. Density functional theory (DFT) calculations demonstrated that the pyridazinedione moiety facilitates cascade rearrangement processes, thereby endowing the key cycloaromatization with a low energy barrier. The enediynes with propargylic oxygen exhibit strong DNA cleavage capabilities, and all pyridazinedione‐fused enediynes showed IC50 values in the range of several tens of micromolars against HeLa cells. [ABSTRACT FROM AUTHOR]

Human coronaviruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pose a serious threat to human life and the global economy. To combat emerging viruses and virus variants, it is essential to develop antivirals with non-specific activities. In this study, we report on the synthesis and antiviral properties of four types of polysulfate-grafted maleimide-based enediyne (EDY) molecules. The sulfates in these EDY molecules are designed to target viruses through non-specific electrostatic interactions, providing extracellular viral targeting ability. Meanwhile, the core EDY generates radical species that disintegrate the viral structure proteins, thereby diminishing the infectivity of coronaviruses. Electron paramagnetic resonance spectroscopy confirmed the radical-generating property of enediynes, while antiviral experiments demonstrated that these enediynes exhibit antiviral activity down to micromolar concentrations, suggesting a promising future for this strategy in developing antiviral drugs. [ABSTRACT FROM AUTHOR]

Crosslinking chemistries occupy an important position in polymer modification with a particular importance when triggered in response to external stimuli. Enediyne (EDY) moieties are used as functional entities in this work, known to undergo a pericyclic Bergman cyclization (BC) to induce a triggered crosslinking of polyurethanes (PU) via the intermediately formed diradicals. Diamino‐EDYs, where the distance between the enyne‐moieties is known to be critical to induce a BC, are placed repetitively as main‐chain structural elements in isophorone‐based PUs to induce reinforcement upon heating, compression, or stretching. A 7‐day compression under room temperature results in a ≈69% activation of the BC, together with the observation of an increase in tensile strength by 62% after 25 stretching cycles. The occurrence of BC is further proven by the decreased exothermic values in differential scanning calorimetry, together with characteristic peaks of the formed benzene moieties via IR spectroscopy. Purely heat‐induced crosslinking contributes to 191% of the maximum tensile strength in comparison to the virgin PU. The BC herein forms an excellent crosslinking strategy, triggered by heat or force in PU materials. [ABSTRACT FROM AUTHOR]

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Under physiological conditions, natural enediynes antibiotics generate free radicals through a cycloaromatization reaction. The resulting highly reactive radicals can abstract hydrogen atoms on the phosphate backbone of DNA, leading to high cytotoxicity. On the other hand, anthraquinone‐fused compounds such as daunomycin and adriamycin can insert into DNA through planar aromatic ring structures, resulting in strong DNA damage. To this end, a series of naphthoquinone‐based enediynes were designed and synthesized by adjusting the type of terminal alkyne to modulate their water solubility and radical generation property. Theoretical calculations suggest that the naphthoquinone‐based enediyne generates radicals through a rearrangement (1,3‐proton transfer) followed by Myers‐Saito cyclization processes, with a much lower activation free energy barrier than Bergman cyclization (24.2 kcal/mol vs 39.8 kcal/mol). Differential scanning calorimetry and electron paramagnetic resonance results showed that naphthoquinone‐based enediynes undergo cycloaromatization at relatively low temperatures, resulting in the generation of highly reactive radical species. The enediynes with optimal water solubility displayed strong DNA cleavage ability at micromolar level and high cytotoxicity towards Hela cells, providing a half‐inhibitory concentration of 8.19 μM. [ABSTRACT FROM AUTHOR]

Four new chlorinated cycloaromatized enediyne compounds, jejucarbosides B–E (1–4), were discovered together with previously-identified jejucarboside A from a marine actinomycete strain. Compounds 1–4 were identified as new chlorinated cyclopenta[a]indene glycosides based on 1D and 2D nuclear magnetic resonance, high-resolution mass spectrometry, and circular dichroism (CD) spectra. Jejucarbosides B and E bear a carbonate functional group whereas jejucarbosides C and D are variants possessing 1,2-diol by losing the carbonate functionality. It is proposed that the production of 1–4 occurs via Bergman cycloaromatization capturing Cl- and H+ in the alternative positions of a p-benzyne intermediate derived from a 9-membered enediyne core. Jejucarboside E (4) displayed significant cytotoxicity against human cancer cell lines including SNU-638, SK-HEP-1, A549, HCT116, and MDA-MB-231, with IC50 values of 0.31, 0.40, 0.25, 0.29, and 0.48 μM, respectively, while jejucarbosides B–D (1–3) showed moderate or no cytotoxic effects. [ABSTRACT FROM AUTHOR]

Radiomimetic compounds, similarly to ionising radiation can directly or indirectly cause DNA damage. Two major groups of these compounds, alkylating agents and antimetabolites, have already been discussed in the first part of this article. The topic of this article is an overview of radiomimetic substances of biological origin; they are grouped and discussed upon their chemical structure. Some bacteria, belonging to the class of Actinobacteria can produce compounds with radiomimetic property as part of their defence mechanisms, such as bleomycins, enediynes, streptonigrins, etc. Radiomimetic compounds of bacterial origin can be divided into three main groups: radiomimetic glycopeptides, enediynes and quinone antibiotics. Each of them induces double-strand DNA breaks. Some of them work through their reactive radicals and the molecules are also transformed when they break DNA. Others, such as bleomycin and similar glycopeptides, have an enzyme-like catalytic effect as the molecule regenerates itself after interacting with DNA thus the same molecule can create new DNA breaks again. The damage caused by radiation and by bleomycin is very similar: double DNA strand breaks occur in close proximity to each other, below the lethal dose of the cell, so as the cell does not die, the DNA repair process is activated, which can lead to the formation of dicentric chromosomes and other detectable DNA alterations. This review briefly summarises the mechanism of action of bacterial radiomimetic compounds and their benefit. [ABSTRACT FROM AUTHOR]

The enediynes are structurally characterized by a 1,5-diyne-3-ene motif within a 9- or 10-membered enediyne core. The anthraquinone-fused enediynes (AFEs) are a subclass of 10-membered enediynes that contain an anthraquinone moiety fused to the enediyne core as exemplified by dynemicins and tiancimycins. A conserved iterative type I polyketide synthase (PKSE) is known to initiate the biosynthesis of all enediyne cores, and evidence has recently been reported to suggest that the anthraquinone moiety also originates from the PKSE product. However, the identity of the PKSE product that is converted to the enediyne core or anthraquinone moiety has not been established. Here, we report the utilization of recombinant E. coli coexpressing various combinations of genes that encode a PKSE and a thioesterase (TE) from either 9- or 10-membered enediyne biosynthetic gene clusters to chemically complement ΔPKSE mutant strains of the producers of dynemicins and tiancimycins. Additionally, 13C-labeling experiments were performed to track the fate of the PKSE/TE product in the ΔPKSE mutants. These studies reveal that 1,3,5,7,9,11,13-pentadecaheptaene is the nascent, discrete product of the PKSE/TE that is converted to the enediyne core. Furthermore, a second molecule of 1,3,5,7,9,11,13-pentadecaheptaene is demonstrated to serve as the precursor of the anthraquinone moiety. The results establish a unified biosynthetic paradigm for AFEs, solidify an unprecedented biosynthetic logic for aromatic polyketides, and have implications for the biosynthesis of not only AFEs but all enediynes. [ABSTRACT FROM AUTHOR]

We report a transition metal‐free, regio‐ and stereo‐selective, phosphine‐catalyzed method for the trans hydroboration of 1,3‐diynes with pinacolborane that affords (E)‐1‐boryl‐1,3‐enynes. The reaction proceeds with excellent selectivity for boron addition to the external carbon of the 1,3‐diyne framework as unambiguously established by NMR and X‐ray crystallographic studies. The reaction displays a broad substrate scope including unsymmetrical diynes to generate products in high yield (up to 95 %). Experimental and theoretical studies suggest that phosphine attack on the alkyne is a key process in the catalytic cycle. [ABSTRACT FROM AUTHOR]

Four new chlorinated cycloaromatized enediyne compounds, jejucarbosides B–E (1–4), were discovered together with previously-identified jejucarboside A from a marine actinomycete strain. Compounds 1–4 were identified as new chlorinated cyclopenta[a]indene glycosides based on 1D and 2D nuclear magnetic resonance, high-resolution mass spectrometry, and circular dichroism (CD) spectra. Jejucarbosides B and E bear a carbonate functional group whereas jejucarbosides C and D are variants possessing 1,2-diol by losing the carbonate functionality. It is proposed that the production of 1–4 occurs via Bergman cycloaromatization capturing Cl- and H+ in the alternative positions of a p-benzyne intermediate derived from a 9-membered enediyne core. Jejucarboside E (4) displayed significant cytotoxicity against human cancer cell lines including SNU-638, SK-HEP-1, A549, HCT116, and MDA-MB-231, with IC50 values of 0.31, 0.40, 0.25, 0.29, and 0.48 μM, respectively, while jejucarbosides B–D (1–3) showed moderate or no cytotoxic effects.

The prochiral 4-(allyloxy)hepta-1,6-diynes, optionally modified in the positions 1 and 7 with an alkyl or ester group, undergo a chemoselective ring-closing enyne metathesis yielding racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans. Among the catalysts tested, Grubbs 1st generation precatalyst in the presence of ethene (Mori conditions) gave superior results compared to the more stable Grubbs or Hoveyda–Grubbs 2nd generation precatalysts. This is probably caused by a suppression of the subsequent side-reactions of the enyne metathesis product with ethene. On the other hand, the 2nd generation precatalysts gave better yields in the absence of ethene. The metathesis products, containing both a triple bond and a conjugated system, can be successfully orthogonally modified. For example, the metathesis product of 5-(allyloxy)nona-2,7-diyne reacted chemo- and stereoselectively in a Diels–Alder reaction with N-phenylmaleimide affording the tricyclic products as a mixture of two separable diastereoisomers, the configuration of which was estimated by DFT computations. The reported enediyne metathesis paves the way to the enantioselective enyne metathesis yielding chiral building blocks for compounds with potential biological activity, e.g., norsalvinorin or cacospongionolide B.

The Nicholas-type macrocyclization through NH-tosyl functional group has been found to be an efficient technique for the synthesis of a 10-membered azaenediyne system annulated with a benzothiophene. To compare the activity of azaenediyne synthesized with similar oxa- and carbocyclic enediynes the Bergman cyclization activation energies and the ability of enediynes to cleave DNA (pBR322 plasmid) were investigated. The order of reactivity predicted by DFT calculations (N-enediyne < C-enediyne < O-enediyne) was confirmed by DSC analysis data. Surprisingly azaenediyne was found to be more active in the DNA cleavage assay than the C-analogue. [ABSTRACT FROM AUTHOR]

Abstract Enediyne cytotoxic drugs have attracted much attention because of their unique structure and potent anticancer activity. However, acyclic enediynes are long considered as inactive at physiological temperature due to their long C1-C6 distance. By adjusting the steric bulkiness of the functional groups at the alkynyl termini and the electron-withdrawing effect at the ene moiety, herein, a simple acyclic enediyne was designed and synthesized to achieve the onset of thermal Bergman cyclization at physiological temperature in polar solvents. The spontaneous generation of diradical intermediates was confirmed through EPR analysis and further supported by spin trapping experiment, radical indicator experiment, and high resolution MS analysis. The reactive diradicals generated in aqueous media induced single and double stranded cleavage of DNA, and showed high cytotoxicity to Hela cells. The IC 50 value of the enediyne compound is comparable to many clinical used anti-tumor agents. Graphical abstract An acyclic enediyne functions possibly through spontaneous Bergman cyclization to induce DNA cleavage, inhibit cancer cell growth, and lead cancer cells to apoptosis pathway. Image 1 [ABSTRACT FROM AUTHOR]

The discovery of anti-tumor antibiotics like neocarcinostatin class has prompted a great deal of research to reconstruct their total synthesis or to search for similar simple structures with comparable biologic activities. The (Z)- hept-4-ene-2,6-diynylmethylether is one of the precursors. It is obtained by successive coupling reactions of acetylenic compounds in the presence of palladium (o). The high cost of this catalyst and the environmental requirements limiting the use of metal, led us to seek an alternative to access this precursor compound. The approach we have developed consists of the dehydration of diynols to generate the yne-ene-yne sequence with (Z) configuration. The diynols are obtained by a propargyl Grignard reaction on the corresponding aldehydes. The aldehydes are themselves obtained by oxidation of the appropriate alcohols. Another way developed in this work was to obtain the aldehydes by formylation of propargyletheracetylide. We have thus synthesized (Z)-hept-4-ene-2,6-diynylmethylether and its benzyl-substituted analogue. The dehydration reaction is accompanied by configuration isomers (E). The overall yield is of the order of 30% but it is possible to prepare large quantities of product according to these methods. [ABSTRACT FROM AUTHOR]

The coupling of two equivalents of ethynylferrocene (2) with one equivalent of 1,2-diiodocyclohexene (1) and 1,2-diiodobenzene (4) using Sonogashira cross-coupling conditions led to 1,2-bis(ferrocenylethynyl)cyclohexene (3) and 1,2-bis(ferrocenylethy­nyl)benzene (5), respectively. At high temperatures enediynes 3 and 5 showed exothermic signals in differential scanning calorimetry (DSC) measurements, suggestive of intramolecular diradicaloid ring formation (Bergman (C1−C6) or Schreiner-Pascal (C1−C5) cyclizations). The oxidation of 3 and 5 to the mono-oxidized enediynes 3+ and 5+ decreased the onset temperatures drastically. Equally, 1-ferrocenylethynyl-2-(p-nitro-phenyl)ethynylbenzene (8) displayed a significant decrease in the onset temperature after oxidation to 8+. Because the insoluble nature of the polymeric material formed in the thermolysis of the oxidized enediynes prevented characterization, the origin of this drastic effect was studied by DFT. Contrary to expectations, one-electron oxidation does not lower the barrier for intramolecular cyclization. Rather, the computations suggest that the polymerization is initiated by a bimolecular process.

Bergman cyclization has shown great promise in constructing conjugated polymers. However, the application of this reaction in polymer science is still limited due to the harsh reaction condition and ill-defined structure of the achieved polymers. To this end, the cycloaromatization polymerization of enediynes catalyzed by a series of transition metal catalysts is investigated in this work, by taking advantage of the coordination chemistry of the enediyne with the transition metal complexes. According to the nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR), ultraviolet-visble (UV-Vis) spectroscopies and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis, the cycloaromatization polymerization of enediynes proceeds under milder conditions and in a more controlled manner in the presence of palladium(II) complexes, giving structurally regulated conjugated polymers in high yields. [ABSTRACT FROM AUTHOR]

Three kinds of AB2 type monomers with terminal alkyne (A) and iodine (B) were synthesized from dichloromaleic anhydride by amidation with terminal alkynyl amine followed by chlorine-iodine exchange reaction. Starting from these AB2 monomers, a series of hyperbranched polymers with enediyne repeating unit (HBEPs) were synthesized via one-pot Sonogashira cross coupling polymerization reaction. The structure of these HBEPs was characterized by NMR, FT-IR, GPC, DLS, DSC, UV-Vis and fluorescence spectroscopy. The effects of substituents of backbone on the physical and chemical properties of these polymers were studied. Results show that the maximum degree of branching of HBEPs is close to 1. In addition, the fluorescence characteristics of HBEPs are related to its conjugation degree . [ABSTRACT FROM AUTHOR]

A series of M(PyED)⋅X (X = 2Cl-, SO42-) pyridine-metalloenediyne complexes [M = Cu(II), Fe(II), or Zn(II)] and their independently synthesized, cyclized analogs have been prepared to investigate their potential as radical-generating DNA-damaging agents. All complexes possess a 1:1 metal-to-ligand stoichiometry as determined by electronic absorption spectroscopy and X-ray diffraction. Solution structural analysis reveals a pπ Cl → Cu(II) LMCT (22,026 cm-1) for Cu(PyED)⋅2Cl, indicating three nitrogens and a chloride in the psuedo-equatorial plane with the remaining pyridine nitrogen and solvent in axial positions. EPR spectra of the Cu(II) complexes exhibit an axially elongated octahedron. This spectroscopic evidence, together with density functional theory computed geometries, suggest six-coordinate structures for Cu(II) and Fe(II) complexes and a five-coordinate environment for Zn(II) analogs. Bergman cyclization via thermal activation of these constructs yields benzannulated product indicative of diradical generation in all complexes within 3 h at 37 °C. A significant metal dependence on the rate of the reaction is observed [Cu(II) > Fe(II) > Zn(II)], which is mirrored in in vitro DNA-damaging outcomes. Whereas in situ chelation of PyED leads to considerable degradation in the presence of all metals within 1 h under hyperthermia conditions, Cu(II) activation produces >50% compromised DNA within 5 min. Additionally, Cu(II) chelated PyED outcompetes DNA polymerase I to successfully inhibit template strand extension. Exposure of HeLa cells to Cu(PyBD)⋅SO4 (IC50 = 10 µM) results in a G2/M arrest compared with untreated samples, indicating significant DNA damage. These results demonstrate metal-controlled radical generation for degradation of biopolymers under physiologically relevant temperatures on short timescales. [ABSTRACT FROM AUTHOR]

A series of AB 2 type monomers with terminal alkyne (A) and iodine (B) were synthesized from dichloromaleic anhydride by amidation with terminal alkynylamine followed by chlorine-iodine exchange reaction. Starting from these AB 2 monomers, three kinds of fluorescent hyperbranched polymers with enediyne repeating units (HBEP1∼HBEP3) were synthesized via one-pot Sonogashira cross coupling polymerization reaction. The HBEPs was characterized by a variety of techniques and the degree of branching (DB) of the HBEPs were determined by 1 H NMR spectroscopy. The molecular weights ( M n ) of HBEPs are up to 73 kDa and the DBs are up to 0.97, close to that for a dendrimer. Due to the different degree of conjugation of these HBEPs, the HBEPs display different photo-luminescence and excitation-dependent fluorescence behavior. These HBEPs were further subjected to thermal Bergman cyclization to generate crosslinked polymeric networks with spatially locked persistent radicals. EPR experiments showed that the free radicals in these materials were stable for a long time at room temperature and can be slowly quenched when exposed to air, providing a promising application as long-term free radical cleaner. [ABSTRACT FROM AUTHOR]

Enediyne compounds generally undergo a Bergman cyclization reaction under photo-irradiation conditions. In this study, we observed an unexpected [2+2] photo-cycloaddition between enediyne compounds under photo-irradiation conditions. The structure of the cycloaddition product was confirmed through NMR, HR-MS and single crystal XRD analyses. The cycloaddition was only preferred when the reaction was conducted in the solid state or under highly concentrated conditions in the solution state. In contrast, the use of dilute conditions favored the Bergman cyclization. The concentration dependence of the enediyne substrate was further confirmed by EPR and MALDI-TOF analyses of the products. Computational investigations showed that the initial step would involve the formation of a [4+4] dimer structure, which would be converted to the [2+2] product in the second step. Interestingly, the [2+2] reaction was found to be reversible back to the enediyne monomer, where it could undergo a photo-Bergman cyclization under diluted conditions, thereby providing a new method for the formation of 'masked' enediynes for further applications. [ABSTRACT FROM AUTHOR]

Bergman cyclization, an organic reaction that forms 1,4-benzene diradicals via intramolecular cyclization of enediyne (EDY) compounds, is a fascinating reaction and can be used to fabricate polyarylenes with various side chains and construct carbon nanomaterials with diverse morphologies. Bergman cyclization has had a strong impact on a number of fields, including pharmaceutics, polymer chemistry, and materials science. The homopolymerization of EDYs through Bergman cyclization is an ingenious strategy for fabrication of functional polyarylenes and has the advantages of facial operation, high efficiency, tailored structure, and being catalyst-free. Moreover, the obtained functionalized polyarylenes show many remarkable properties, such as excellent thermal stability, good solubility, and processability, which enable these polyarylenes to be further manufactured into carbon nanomaterials. Recently, extensive efforts have been devoted to the application of Bergman cyclization in polymer chemistry, materials science, and nanodevices. This chapter summarizes the synthetic strategies that have been developed for fabrication of structurally unique carbon-rich materials using Bergman cyclization, including formation of nanoparticles by intramolecular collapse of single polymer chains, fabrication of conjugated microporous polymers, and construction of carbon nanomembranes with different morphologies and their applications in nanodevices. The future development of Bergman cyclization in materials science is discussed, especially in the construction and application of carbon nanomaterials by altering the template types and morphologies to precisely control the microstructures and properties of carbon nanomaterials. [ABSTRACT FROM AUTHOR]

Treatment of readily prepared (Z)-6-benzyloxy-1,1,1,2-tetrafluoro-6-methyl-2-hepten-4-yne with 1.5 equiv of LHMDS in −78 °C for 1 h gave the corresponding trifluoromethylated diyne in an excellent yield. This diyne was found to be a good substrate for the carbocupration with various higher-ordered cyanocuprates to give the corresponding vinylcuprates in a highly regio- and stereoselective manner. The in situ generated vinylcuprates could react very smoothly with an excess amount of iodine, the vinyl iodides being obtained in high yields. Thus-obtained iodides underwent a very smooth Sonogashira cross-coupling reaction to afford various trans-enediynes in high yields.

The compounds produced by a living organism are most commonly as medicinal agents and starting materials for the preparation of new semi-synthetic derivatives. One of the largest groups of natural compounds consists of products containing a 1,4-benzoquinone subunit. This fragment occurs in three enediyne antibiotics, dynemicin A, deoxydynemicin A, and uncilamicin, which exhibit high biological activity. A series of alkoxy derivatives containing 1,4-naphthoquinone, 5,8-quinolinedione, and 2-methyl-5,8-quinolinedione moieties was synthesized. Moreover, the 1,4-benzoquinone subunit was contacted with an enediyne fragment. All obtained compounds were characterized by spectroscopy and spectrometry methods. The resulting alkane, alkene, alkyne and enediyne derivatives were tested as antitumor agents. They showed high cytotoxic activity depending on the type of 1,4-benzoquinone subunit and the employed tumor cell lines. The synthesized derivatives fulfill the Lipinski Rule of Five and have low permeability through the blood-brain barrier. [ABSTRACT FROM AUTHOR]

Conjugation of cancer targeting peptides (CTPs) with small molecular therapeutics has emerged as a promising strategy to deliver potent (but typically nonspecific) cytotoxic agents selectively to cancer cells. Here we report the engineered production of a CTP (NGR)-containing C-1027 and evaluation of its activity against selected cancer cell lines. C-1027 is an enediyne chromoprotein produced by Streptomyces globisporus , consisting of an apo-protein (CagA) and an enediyne chromophore (C-1027). NGR is a CTP that targets CD13 in tumor vasculature. S. globisporus SB1026, a recombinant strain engineered to encode CagA with the NGR sequence fused at its C-terminus, directly produces the NGR-containing C-1027 that is equally active as the native C-1027. Our results demonstrate the feasibility to produce CTP-containing enediyne chromoproteins by metabolic pathway engineering and microbial fermentation and will inspire efforts to engineer other CTP-containing drug binding proteins for targeted delivery. [ABSTRACT FROM AUTHOR]

ABSTRACT We report the synthesis and characterization of a unique class of conjugated polymers, polytriacetyelenes (PTAs), from a set of trans-enediyne (EDY) monomers bearing alkyl and aromatic substituents. Two different methods, i.e., Glaser-Hay coupling and Pd-catalyzed oxidative coupling, were employed depending on the nature of the side-chains. Our methodology is highly versatile in that it allows direct attachment of aromatic substituents to the PTA main-chains, allowing enhanced tunability in polymer electronic properties, which has not been achievable through previously reported methods. The newly synthesized PTAs displayed strong ability of quenching the fluorescence of poly(3-hexylthiophene) (P3HT), a prototypical conjugated polymer in organic solar cells, indicating possible applications of these PTAs in optoelectronic devices. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 1391-1395 [ABSTRACT FROM AUTHOR]

Background: Calicheamicins (CAL) are enedyine natural products with potent antibiotic and cytotoxic activity, used in anticancer therapy. The O-methyltransferase CalO6 is proposed to catalyze methylation of the hydroxyl moiety at the C2 position of the orsellinic acid group of CAL. Results: Crystals of CalO6 diffracted non-isotropically, with the usable data extending to 3.4 Å. While no single method of crystal structure determination yielded a structure of CalO6, we were able to determine its structure by using molecular replacement-guided single wavelength anomalous dispersion by using diffraction data from native crystals of CalO6 and a highly non-isomorphous mercury derivative. The structure of CalO6 reveals the methyltransferase fold and dimeric organization characteristic of small molecule O-methyltransferases involved in secondary metabolism in bacteria and plants. Uncommonly, CalO6 was crystallized in the absence of S-adenosylmethionine (SAM; the methyl donor) or S-adenosylhomocysteine (SAH; its product). Conclusions: Likely as a consequence of the dynamic nature of CalO6 in the absence of its cofactor, the central region of CalO6, which forms a helical lid-like structure near the active site in CalO6 and similar enzymes, is not observed in the electron density. We propose that this region controls the entry of SAM into and the exit of SAH from the active site of CalO6 and shapes the active site for substrate binding and catalysis. [ABSTRACT FROM AUTHOR]

Chiral enediynes with pendant chiral amino ester groups are synthesized through Sonogashira reactions and subjected to thermal triggered Bergman cyclization at elevated temperatures either in bulk or in solvents to produce chiral polyphenylenes. The disappearance of enediyne monomers are evidenced by FTIR and NMR spectroscopies. The formation of polyphenylenes is further confirmed by UV-Vis and MALDI-TOF mass spectroscopies (MS). Isotope pattern analysis of the MS spectra shows that the polymers prepared in solvents are terminated by the solvent molecules, whereas the chain ends of the polymers prepared in bulk consist of considerable amount of unmasked free radicals, which is further confirmed by EPR analysis. Circular dichroism (CD) spectra of the chiral polymers show blue shifts of the Cotton peaks, indicating the occurrence of the cycloaromatization reaction. A new set of peaks mirrored at the horizontal axis show up in the long wavelength range, which are assigned to main chain chirality of the polyphenylenes. [ABSTRACT FROM AUTHOR]