Organic & Biomolecular Chemistry (v.13, #6)
Front cover (1579-1579).
Inside front cover (1580-1580).
Contents list (1581-1591).
Fixation of sulfur dioxide into small molecules by Gang Liu; Congbin Fan; Jie Wu (1592-1599).
Sulfonyl-derived functional groups can be found in a broad range of natural products, pharmaceuticals, and materials. Among the methods for the introduction of the sulfonyl group into small molecules, the approach using sulfur dioxide is the most promising and attractive one. In the past several years, the insertion of sulfur dioxide into small molecules under transition metal catalysis or metal-free conditions via a radical process has been developed. In this review, recent advances in the insertion of sulfur dioxide are presented.
N-Phosphonyl/phosphinyl imines and group-assisted purification (GAP) chemistry/technology by Guanghui An; Cole Seifert; Guigen Li (1600-1617).
The development of environmentally benign, operationally simple, and economically viable synthetic methodologies has been a great challenge in organic synthesis. Group-assisted purification (GAP) chemistry was established to enable the synthesis of organic compounds without using traditional purification technologies, such as column chromatography and recrystallization. This concept/technology should encourage the synthetic community to make more efforts on searching for environmentally benign reagents and reactions to reduce the waste generated from silica and solvents, particularly toxic solvents; also, to reduce production/synthesis expenses, manpower, and energy. This review will discuss the GAP concept/technology and related reactions that were mainly conducted in the PI's laboratories after 2010.
Divergolide congeners illuminate alternative reaction channels for ansamycin diversification by Ling Ding; Jakob Franke; Christian Hertweck (1618-1623).
Isolation and structure elucidation of six new divergolides reveal unusual ansamycin diversification reactions including formation of the unusual isobutenyl side chain from a branched polyketide synthase extender unit, azepinone ring closure, macrolide ring contraction and formation of a seco variant by a neighboring group-assisted decarboxylation.
Studies towards asymmetric synthesis of 4(S)-11-dihydroxydocosahexaenoic acid (diHDHA) featuring cross-coupling of chiral stannane under mild conditions by Rui Wang; John R. Falck (1624-1628).
An efficient and asymmetric synthetic approach towards one of the biologically interesting 4(S)-11-diHDHA derivatives was developed. This process mainly relied on two reactions, one is the copper-catalyzed mild cross-coupling that allows for the efficient construction of a chiral α-alkynyl α-hydroxy motif and another is the synthesis of chiral α-hydroxy α-stannanes that has previously been developed by our group featuring the asymmetric stannylation using the well-established tributyltin hydride/diethyl zinc system from an aldehyde.
A short, rigid linker between pyrene and guanidiniocarbonyl-pyrrole induced a new set of spectroscopic responses to the ds-DNA secondary structure by Marijana Radić Stojković; Patryciusz Piotrowski; Carsten Schmuck; Ivo Piantanida (1629-1633).
A novel pyrene-guanidiniocarbonyl-pyrrole dye, characterised by a short, rigid linker between the two chromophores, interacts strongly with ds-DNA but only negligibly with ds-RNA. Under neutral conditions the dye shows strong selectivity toward AT-DNA (with respect to GC-DNA). Binding is accompanied by a specific ICD band at 350 nm and fluorescence quenching for all DNAs/RNAs studied. At pH 5 the affinity of the dye is reversed, now favouring GC-DNA over AT-DNA. A strong emission increase for AT-DNA is observed but with quenching for GC-DNA.
Chemoenzymatic flow cascade for the synthesis of protected mandelonitrile derivatives by Mariëlle M. E. Delville; Kaspar Koch; Jan C. M. van Hest; Floris P. J. T. Rutjes (1634-1638).
A chemoenzymatic two-step cascade process, with both steps having incompatible reaction conditions, was successfully performed in continuous flow. The chemoenzymatic aqueous formation of cyanohydrins was integrated with a subsequent organic phase protection step in a single flow process utilising a membrane-based phase separation module. The wider applicability of our setup was demonstrated with the synthesis of nine protected cyanohydrin derivatives, all obtained in good yields and high to excellent enantioselectivity.
Bacterial patterning controlled by light exposure by Willem A. Velema; Jan Pieter van der Berg; Wiktor Szymanski; Arnold J. M. Driessen; Ben L. Feringa (1639-1642).
Patterning of multiple bacterial strains in one system is achieved by employing a single photo-activated antibiotic. Varying the light-exposure time results in zones with mixed and single populations.
Construction of the tricyclic core of steenkrotin-type diterpenoids via intramolecular [3 + 2] cycloaddition by Jun Xuan; Saiyong Pan; Yuanbao Zhang; Bin Ye; Hanfeng Ding (1643-1646).
A concise and diastereoselective route to the angularly fused [5–6–7] tricyclic carbon framework of the steenkrotin-type diterpenoids was reported. The key features of the strategy are based on an intramolecular nitrile oxide/alkene [3 + 2] cycloaddition and a regio-selective aldol/dehydration sequence.
Molecular recognition of upper rim functionalized cavitand and its unique dimeric capsule in the solid state by Mutsumi Kobayashi; Mei Takatsuka; Ryo Sekiya; Takeharu Haino (1647-1653).
Cavitand 1 possesses four 2,2′-bipyridyl pillars on its upper rim that encapsulates small guests, such as nitromethane, acetonitrile, methyl acetate, ethyl acetate, and N-methylacetamide, into a deep cavity to form host–guest complexes in a 1 : 1 ratio. Nitroethane, N,N-dimethylformamide, and N,N-dimethylacetamide were not bound in this manner. A guest-binding study and molecular mechanics calculations revealed that the four 2,2′-bipyridyl pillars of cavitand 1 created a steric boundary that is responsible for selective guest recognition. In the solid state, cavitand 2 formed a unique chiral capsule 22 by π–π stacking interactions between the 2,2′-bipyridyl pillars. A nitromethane molecule was unusually placed deep inside the cavity, as directed by the multiple hydrogen bonding interactions between the nitromethane oxygen atoms, the C–H bonds of the bridge methylenes and the pillar phenyl groups.
Anion binding and transport properties of cyclic 2,6-bis(1,2,3-triazol-1-yl)pyridines by Tamara Merckx; Cally J. E. Haynes; Louise E. Karagiannidis; Harriet J. Clarke; Katie Holder; Alexandra Kelly; Graham J. Tizzard; Simon J. Coles; Peter Verwilst; Philip A. Gale; Wim Dehaen (1654-1661).
A series of cyclic 2,6-bis-(1,2,3-triazolyl)-pyridine anion receptors with thiourea functionalities were synthesized by click reaction of 2,6-diazidopyridine with protected propargylamine followed by condensation of a bisthiocyanate derivative with a series of diamines. Their chloride binding affinities as well as their transport properties in POPC bilayers were examined. These receptors were found to function as anion carriers, which can mediate both Cl−/NO3− antiport and H+/Cl− symport, and the transport activity of these hosts were dominated by their lipophilicity.
UV-visible and 1H–15N NMR spectroscopic studies of colorimetric thiosemicarbazide anion sensors by Kristina N. Farrugia; Damjan Makuc; Agnieszka Podborska; Konrad Szaciłowski; Janez Plavec; David C. Magri (1662-1672).
Four model thiosemicarbazide anion chemosensors containing three N–H bonds, substituted with phenyl and/or 4-nitrophenyl units, were synthesised and studied for their anion binding abilities with hydroxide, fluoride, acetate, dihydrogen phosphate and chloride. The anion binding properties were studied in DMSO and 9 : 1 DMSO–H2O by UV-visible absorption and 1H/13C/15N NMR spectroscopic techniques and corroborated with DFT studies. Significant changes were observed in the UV-visible absorption spectra with all anions, except for chloride, accompanied by dramatic colour changes visible to the naked eye. These changes were determined to be due to the deprotonation of the central N–H proton and not due to hydrogen bonding based on 1H/15N NMR titration studies with acetate in DMSO-d6–0.5% water. Direct evidence for deprotonation was confirmed by the disappearance of the central thiourea proton and the formation of acetic acid. DFT and charge distribution calculations suggest that for all four compounds the central N–H proton is the most acidic. Hence, the anion chemosensors operate by a deprotonation mechanism of the central N–H proton rather than by hydrogen bonding as is often reported.
Reactivity of aldehydes at the air–water interface. Insights from molecular dynamics simulations and ab initio calculations by Marilia T. C. Martins-Costa; Francisco F. García-Prieto; Manuel F. Ruiz-López (1673-1679).
Understanding the influence of solute–solvent interactions on chemical reactivity has been a subject of intense research in the last few decades. Theoretical studies have focused on bulk solvation phenomena and a variety of models and methods have been developed that are now widely used by both theoreticians and experimentalists. Much less attention has been paid, however, to processes that occur at liquid interfaces despite the important role such interfaces play in chemistry and biology. In this study, we have carried out sequential molecular dynamics simulations and quantum mechanical calculations to analyse the influence of the air–water interface on the reactivity of formaldehyde, acetaldehyde and benzaldehyde, three simple aldehydes of atmospheric interest. The calculated free-energy profiles exhibit a minimum at the interface, where the average reactivity indices may display large solvation effects. The study emphasizes the role of solvation dynamics, which are responsible for large fluctuations of some molecular properties. We also show that the photolysis rate constant of benzaldehyde in the range 290–308 nm increases by one order of magnitude at the surface of a water droplet, from 2.7 × 10−5 s−1 in the gas phase to 2.8 × 10−4 s−1 at the air–water interface, and we discuss the potential impact of this result on the chemistry of the troposphere. Experimental data in this domain are still scarce and computer simulations like those presented in this work may provide some insights that can be useful to design new experiments.
Computational study on the intramolecular self-organization of the macrorings of some ‘giant’ cyclodextrins (CDn, n = 40, 70, 85, 100) by Petko M. Ivanov; Emanouil J. Atanassov; Carlos Jaime (1680-1689).
The conformations of some ‘giant’ cyclodextrins (CDn, n = 40, 70, 85, 100) were examined by molecular dynamic simulations using the Glycam06 force field. CD14 and CD26, the largest cyclodextrins, for which crystallographic data are available, were also studied as reference structures. Principal component analysis was used for the analyses of the simulation trajectories. In cases where band-flips were not present in the starting geometry (e.g. CD40), flips appeared later during the conformational search. The results for CDn (n = 14, 26, 40) confirmed an interesting observation for the distribution of band-flips along the perimeters of the macrorings, namely, band-flips separate portions of lengths of about six or twelve glucoses. This allows the formation of energetically favorable small loops of six–seven glucoses or the creation of short two-turns single helices that further enhance the stability of the structures. It was found that flip dihedrals define distributions of fragment lengths 12–6, 12–12, and 12–12–6 residues in the larger CDs (CD70, CD85, CD100). Contributions from 77% (CD40) to 88% (CD26) are from the first three highest-eigenvalue principal components, i.e., a limited number of modes determine the overall deformations of the macrorings. The flexibility of the macrorings increases, going from CD40 to the CDs, with higher degrees of polymerization. CD14 and CD26 present interesting cases – CD26 manifests domination of one deformation mode (ca. 72%), whereas CD14 demonstrates significantly higher flexibility. These results confirm our earlier conclusion, namely, LR-CDs may have more than one cavity. Thus they have the potential to accommodate more than one substrate molecule, as well as larger species by an ‘induced fit’ mechanism.
Preparation of luminescent chemosensors by post-functionalization of vesicle surfaces by Andreas Müller; Burkhard König (1690-1699).
Surface-reactive luminescent vesicles were prepared by self-assembly of phospholipids, amphiphilic maleimides and fluorophors in aqueous solution. Those preformed liposomes were functionalized with various thiolated receptor units using a thiol-click reaction. As recognition elements, a bis-Zn2+-cyclen derivative for the detection of phosphate moieties or a DNA aptamer for the specific binding of the antibiotic ampicillin were utilized. A FRET-based assay revealed the close spatial proximity of the membrane-embedded dansyl molecules with the subsequently immobilized thiols, which is the origin for the signaling mechanism of the obtained vesicular sensors. Those receptor-functionalized liposomes indicate the binding of the targets to their surface by changes of the fluorescence emission properties of the membrane co-embedded carboxyfluorescein dyes. The post-functionalization concept can also be used for molecular imprinting on vesicle surfaces. The template-guided patterning of receptors based on bis-Zn2+-cyclen resulted in fluorescent sensors suitable for the specific recognition of a bivalent peptide.
Highly efficient stabilisation of meta-ethynylpyridine polymers with amide side chains in water by coordination of rare-earth metals by Hiroki Makida; Hajime Abe; Masahiko Inouye (1700-1707).
An amphiphilic meta-ethynylpyridine polymer with chiral amide side chains was developed. The polymer was prepared by sequential Sonogashira reactions, and the product was soluble in polar and apolar solvents. The additive effects of metal salts on the polymer were examined in water and aqueous EtOH on the basis of UV-vis and CD spectra. The enhancement of the positive Cotton effect and hypochromism around 360 nm occurred by the addition of various metal salts, indicating the coordination of the cations to the amide side chains of the polymer to stabilise the helical structure. Among them, rare-earth metal salts, especially Sc(OTf)3 showed more efficient additive effects probably because of its strong coordination ability even in water. Positive cooperativity was observed for the coordination of Sc(OTf)3 to the polymer in aqueous EtOH.
Cyclodextrin- and calixarene-based polycationic amphiphiles as gene delivery systems: a structure–activity relationship study by Laura Gallego-Yerga; Michela Lomazzi; Valentina Franceschi; Francesco Sansone; Carmen Ortiz Mellet; Gaetano Donofrio; Alessandro Casnati; José M. García Fernández (1708-1723).
Multi-head/multi-tail facial amphiphiles built on cyclodextrin (CD) and calixarene (CA) scaffolds are paradigmatic examples of monodisperse gene delivery systems. The possibility to precisely control the architectural features at the molecular level offers unprecedented opportunities for conducting structure–activity relationship studies. A major requirement for those channels is the design of a sufficiently diverse ensemble of compounds for parallel evaluation of their capabilities to condense DNA into transfection nanoparticles where the gene material is protected from the environment. Here we have undertaken the preparation of an oriented library of β-cyclodextrin (βCD) and calixarene (CA4) vectors with facial amphiphilic character designed to ascertain the effect of the cationic head nature (aminothiourea-, arginine- or guanidine-type groups) and the macrocyclic platform on the abilities to complex plasmid DNA (pDNA) and in the efficiency of the resulting nanocomplexes to transfect cells in vitro. The hydrophobic domain, formed by hexanoyl or hexyl chains, remains constant in each series, matching the overall structure found to be optimal in previous studies. DLS, TEM and AFM data support that all the compounds self-assemble in the presence of pDNA through a process that involves initially electrostatic interactions followed by formation of βCD or CA4 bilayers between the oligonucleotide filaments. Spherical transfectious nanoparticles that are monomolecular in DNA are thus obtained. Evaluation in epithelial COS-7 and human rhabdomyosarcoma RD-4 cells evidenced the importance of having primary amino groups in the vector to warrant high levels of transfection, probably because of their buffering capacity. The results indicate that the optimal cationic head depends on the macrocyclic core, aminothiourea groups being preferred in the βCD series and arginine groups in the CA4 series. Whereas the transfection efficiency relationships remain essentially unchanged within each series, irrespective of the cell type, the optimal platform (βD or CA4) strongly depends on the cell type. The results illustrate the potential of monodisperse vector prototypes and diversity-oriented strategies on identifying the optimal candidates for gene therapy applications.
Using Hansen solubility parameters to study the encapsulation of caffeine in MOFs by Lorena Paseta; Grégory Potier; Steven Abbott; Joaquín Coronas (1724-1731).
Hansen solubility parameters (HSP) have found their greatest use in the evaluation of solvent–polymer chemical interactions. Given their great interest among the scientific community, host–guest interactions in metal–organic frameworks (MOFs), with organic and inorganic moieties, could benefit from a HSP approach. In this work we have initiated the application of HSP to the study of caffeine encapsulation in MOFs ZIF-8 and NH2-MIL-88B(Fe). However, the availability of HSP for MOFs is nearly zero. As a first step to evaluating the potential of HSP for rational design we have made the simplifying assumption that the HSP distance of the caffeine–ligand interaction (i.e. ignoring the metal and the MOF structure) dominates the ability to form a MOF host–guest system. Although much work remains to be done, the first indications are that this approach has much potential.
Aryl-bis-(scorpiand)-aza receptors differentiate between nucleotide monophosphates by a combination of aromatic, hydrogen bond and electrostatic interactions by Jorge González-García; Sanja Tomić; Alberto Lopera; Lluís Guijarro; Ivo Piantanida; Enrique García-España (1732-1740).
Bis-polyaza pyridinophane scorpiands bind nucleotides in aqueous medium with 10–100 micromolar affinity, predominantly by electrostatic interactions between nucleotide phosphates and protonated aliphatic amines and assisted by aromatic stacking interactions. The pyridine-scorpiand receptor showed rare selectivity toward CMP with respect to other nucleotides, whereby two orders of magnitude affinity difference between CMP and UMP was the most appealing. The phenanthroline-scorpiand receptor revealed at pH 5 strong selectivity toward AMP with respect to other NMPs, based on the protonation of adenine heterocyclic N1. The results stress that the efficient recognition of small biomolecules within scorpiand-like receptors relies mostly on the electrostatic and H-bonding interactions despite the competitive interactions in the bulk solvent, thus supporting further optimisation of this versatile artificial moiety.
Synthesis, and QSAR analysis of anti-oncological active spiro-alkaloids by Adel S. Girgis; Siva S. Panda; I. S. Ahmed Farag; A. M. El-Shabiny; A. M. Moustafa; Nasser S. M. Ismail; Girinath G. Pillai; Chandramukhi S. Panda; C. Dennis Hall; Alan R. Katritzky (1741-1753).
QSAR study describes the anti-neoplastic spiro-alkaloids with relevant molecular descriptors using CODESSA III software. The dispiro[3H-indole-3,2′-pyrrolidine-3′,3′′-piperidines] 24–48 were synthesized via [3 + 2]-cycloaddition reaction of azomethine ylides, (generated in situ via decarboxylative condensation of isatins 21–23 with sarcosine) and 3E,5E-1-alkyl-3,5-bis(arylmethylidene)-4-piperidones 10–20. Some of the synthesized analogues exhibited promising antitumor properties against HELA (cervical), HEPG2 (liver), T-47D, MCF7 (breast), and HCT116 (colon) human tumor cell lines, demonstrating activity close to or even better than the standard Doxorubicin, based on in vitro Sulfo-Rhodamine-B bio-assay.
Syntheses of arabinose-derived pyrrolidine catalysts and their applications in intramolecular Diels–Alder reactions by Tony K. M. Shing; Kwun W. Wu; Ho T. Wu; Qicai Xiao (1754-1762).
Six chiral hydroxylated pyrrolidine catalysts were synthesized from commercially available d-arabinose in seven steps. Various aromatic substituents α to the amine can be introduced readily by a Grignard reaction, which enables facile optimization of the catalyst performance. The stereoselectivities of these catalysts have been assessed by comparing with those of MacMillan's imidazolidinone in a known intramolecular Diels–Alder (IMDA) reaction of a triene. Two additional IMDA reactions of symmetrical dienals with concomitant desymmetrisation further established the potential use of these novel amine catalysts. These pyrrolidines are valuable catalysts for other synthetic transformations.
A BODIPY-luminol chemiluminescent resonance energy-transfer (CRET) cassette for imaging of cellular superoxide by S. Bag; J.-C. Tseng; J. Rochford (1763-1767).
Spectroscopic and in cellulo studies are here reported on the very first BODIPY-luminol chemiluminescent resonance energy-transfer (CRET) cassette where the luminol CL agent is covalently linked to the BODIPY energy-transfer acceptor in a molecular dyad. The efficiency of intramolecular CRET investigated for the BODIPY-luminol dyad was found to be 64% resulting in a dual emissive response. Successful in cellulo biochemiluminescence via CRET was achieved in PMA activated splenocytes.
A monolith immobilised iridium Cp* catalyst for hydrogen transfer reactions under flow conditions by Maria Victoria Rojo; Lucie Guetzoyan; Ian. R. Baxendale (1768-1777).
An immobilised iridium hydrogen transfer catalyst has been developed for use in flow based processing by incorporation of a ligand into a porous polymeric monolithic flow reactor. The monolithic construct has been used for several redox reductions demonstrating excellent recyclability, good turnover numbers and high chemical stability giving negligible metal leaching over extended periods of use.
Trigonal scaffolds for multivalent targeting of melanocortin receptors by N. G. R. Dayan Elshan; Thanuja Jayasundera; Bobbi L. Anglin; Craig S. Weber; Ronald M. Lynch; Eugene A. Mash (1778-1791).
Melanocortin receptors can be used as biomarkers to detect and possibly treat melanoma. To these ends, molecules bearing one, two, or three copies of the weakly binding ligand MSH(4) were attached to scaffolds based on phloroglucinol, tripropargylamine, and 1,4,7-triazacyclononane by means of the copper-assisted azide–alkyne cyclization. This synthetic design allows rapid assembly of multivalent molecules. The bioactivities of these compounds were evaluated using a competitive binding assay that employed human embryonic kidney cells engineered to overexpress the melanocortin 4 receptor. The divalent molecules exhibited 10- to 30-fold higher levels of inhibition when compared to the corresponding monovalent molecules, consistent with divalent binding. The trivalent molecules were only statistically (∼2-fold) better than the divalent molecules, still consistent with divalent binding but inconsistent with trivalent binding. Possible reasons for these behaviors and planned refinements of the multivalent constructs targeting melanocortin receptors based on these scaffolds are discussed.
Identification of benzenesulfonamide quinoline derivatives as potent HIV-1 replication inhibitors targeting Rev protein by Fudi Zhong; Guannan Geng; Bing Chen; Ting Pan; Qianwen Li; Hui Zhang; Chuan Bai (1792-1799).
Human immunodeficiency virus type 1 (HIV-1) Rev protein facilitates the export of viral RNA from nucleus to cytoplasm, which is a key step in HIV-1 pathogenesis and transmission. In this study, we have screened a commercial library and identified the hit compound 1 bearing a benzenesulfonamide quinoline scaffold that inhibited Rev activity and HIV-1 infectivity. Compounds bearing this scaffold were synthesized and their SAR was studied. We identified compound 20 with low toxicity and potent activity to inhibit HIV-1 replication by affecting Rev function.
Multicomponent one-pot synthesis of highly-functionalized pyrrole-3-carbonitriles in aqueous medium and their computational study by Ramakanth Pagadala; Devendar Reddy Kommidi; Shravankumar Kankala; Suresh Maddila; Parvesh Singh; Brenda Moodley; N. A. Koorbanally; Sreekantha B. Jonnalagadda (1800-1806).
A one-pot green protocol involving four-components in aqueous medium is developed to synthesize highly-functionalized pyrroles in good yields. Two of the newly synthesized compounds were subjected to in silico analysis on the Pharm Mapper web-server and the human mitogen-activated protein kinase1 (MEK1) enzyme was identified as a potential target protein for these compounds. For target validation, MEK-1 inhibition was performed with two representative compounds (5g and 5h) using docking simulations. These functionalized pyrroles were also tested for their respective IC50 values on human cancer cell lines to evaluate their biocompatibility. Several of these functionalized pyrrole molecules were found to possess higher growth inhibition activity than standard doxorubicin and cisplatin.
An asymmetric pericyclic cascade approach to 3-alkyl-3-aryloxindoles: generality, applications and mechanistic investigations by Edward Richmond; Kenneth B. Ling; Nicolas Duguet; Lois B. Manton; Nihan Çelebi-Ölçüm; Yu-Hong Lam; Sezen Alsancak; Alexandra M. Z. Slawin; K. N. Houk; Andrew D. Smith (1807-1817).
The reaction of l-serine derived N-arylnitrones with alkylarylketenes generates asymmetric 3-alkyl-3-aryloxindoles in good to excellent yields (up to 93%) and excellent enantioselectivity (up to 98% ee) via a pericyclic cascade process. The optimization, scope and applications of this transformation are reported, alongside further synthetic and computational investigations. The preparation of the enantiomer of a Roche anti-cancer agent (RO4999200) 1 (96% ee) in three steps demonstrates the potential utility of this methodology.
Amphiphilic benzothiadiazole–triphenylamine-based aggregates that emit red light in water by Tsutomu Ishi-i; Ikumi Kitahara; Shimpei Yamada; Yusuke Sanada; Kazuo Sakurai; Asami Tanaka; Naoya Hasebe; Toshitada Yoshihara; Seiji Tobita (1818-1828).
In this study, we report a preparation and an aggregate emission behavior of an amphiphilic donor–acceptor dye, which is composed of a triphenylamine–benzothiadiazole donor–acceptor chromophore and two water-soluble hexa(ethylene glycol) chains. The dye is strongly fluorescent in nonpolar solutions such as cyclohexane and toluene, whereas the emission intensity is reduced in aprotic polar solutions such as DMF and acetonitrile. This fluorescence reduction correlates with the increase in polarity, by which the transition from a local excited state to a highly polarized excited state is facilitated, leading to an increased nonradiative deactivation rate. Furthermore, significant fluorescence quenching is observed in protic polar solutions such as ethanol and methanol. Hydrogen-bonding interactions between the dye and the protic solvent molecules further accelerate the deactivation rate. In contrast, in a water solution, red light emission is achieved distinctly at 622 nm with a relatively large fluorescence quantum yield of 0.20. This red emission is related to the aggregation of the dye molecules grown in water. The kinetic analysis from the fluorescence rate constant and nonradiative rate constant indicates that the nonradiative deactivation channel is restricted in water. The formed aggregate, which was indicated by transmittance electron microscopy as a spherical aggregate morphology with a diameter of 3–4 nm, provides a less polar hydrophobic space inside the aggregate structure, by which hydrogen-bonding and the subsequent quenching are restricted, leading to the reduction of the nonradiative deactivation rate.
N-heterocyclic carbene-catalyzed [4 + 2] cyclization of 2-bromo-2-enal with 3-alkylenyloxindoles: efficient assembly of spirocarbocyclic oxindole by Yuanwei Xie; Yonglei Que; Tuanjie Li; Ling Zhu; Chenxia Yu; Changsheng Yao (1829-1835).
A NHC-catalyzed [4 + 2] cyclization of 2-bromo-2-enal bearing γ-H with 3-alkylenyloxindoles under mild reaction conditions gives spirocarbocyclic oxindoles containing one quaternary carbon in moderate to good yields with high diastereoselectivities. The easy availability of the starting materials, the concise assembly and the potential utilization value of the products make this strategy attractive in molecular biology and pharmacy.
Ambient temperature synthesis of β,β′-fused nickel(ii) pyrrolo[1,2-a]pyrazinoporphyrins via a DBSA-catalyzed Pictet–Spengler approach by Dileep Kumar Singh; Mahendra Nath (1836-1845).
A facile first synthetic strategy to construct novel π-extended β,β′-fused nickel(ii) pyrrolo[1,2-a]pyrazinoporphyrins has been developed via a Pictet–Spengler reaction of newly prepared nickel(ii) 2-amino-3-(pyrrol-1-yl)-5,10,15,20-tetraphenylporphyrin with various aromatic, aliphatic or heterocyclic aldehydes in the presence of 10 mol% p-dodecylbenzenesulfonic acid (DBSA) as an efficient Brønsted acid catalyst in 1,4-dioxane at 25 °C. A variety of these π-extended porphyrin analogues were obtained in moderate to good yields under mild conditions and characterized on the basis of spectral data and single crystal X-ray analysis.
Studies towards the synthesis of bielschowskysin. Construction of the highly functionalized bicyclo[3.2.0]heptane segment by Anupam Jana; Sujit Mondal; Subrata Ghosh (1846-1859).
A stereocontrolled approach for the construction of a highly functionalized bicyclo[3.2.0]heptane derivative embodying the bridged lactone present in the diterpene bielschowskysin is reported. The key step involves a stereoselective Cu(i)-catalyzed [2 + 2] photocycloaddition of a 1,6-diene embedded in a sugar derivative.
Phosphate binding by a novel Zn(ii) complex featuring a trans-1,2-diaminocyclohexane ligand. Effective anion recognition in water by Oscar Francesconi; Matteo Gentili; Francesco Bartoli; Andrea Bencini; Luca Conti; Claudia Giorgi; Stefano Roelens (1860-1868).
In this work we have investigated the binding properties of a new synthetic receptor for phosphate anions that combines metal ion coordination with electrostatic and H-bonding interactions. The described receptor is obtained by assembling an iminodiacetic (IDA) fragment, as a Zn(ii) binding site, with a polyamine macrocyclic portion containing two trans-1,2-diaminocyclohexane (DAC) units and a pyrrole ring, as a cationic binding site, into an adaptive structure appropriately spanning the length of di- and tridentate phosphates. Potentiometric measurements together with 1H and 31P NMR investigation showed that, in a wide pH range including values of physiological interest, the Zn(ii) complex of the receptor binds di- and triphosphates, such as ADP, ATP, pyrophosphate (PP) and triphosphate (TP), far better than monophosphate (MP), and that TP is poorly bound by methyliminodiacetate (MIDA) as a model for the Zn(ii) binding site. Besides the excellent selectivity over other phosphates, the affinity for TP is the largest reported to date for Zn(ii) complexes in water.
Differentiation of small alkane and alkyl halide constitutional isomers via encapsulation by Matthew R. Sullivan; Bruce C. Gibb (1869-1877).
Previously we have demonstrated that host 1 is capable of hydrocarbon gas separation by selective sequestration of butane from a mixture with propane in the headspace above a solution of the host (C. L. D. Gibb, B. C. Gibb, J. Am. Chem. Soc., 2006, 128, 16498–16499). Expanding on the idea of using this host as a means to affect guest discrimination, we report here on NMR studies of the binding of constitutional isomers of two classes of small molecules: hexanes and chloropentanes. Our results indicate that even with these relatively straightforward classes of molecules, guest binding is complicated. Overall, host 1 displays a preference to bind guests with a X–C(R2)–C(R2)–Me (X = Cl or Me) structure, and more generally, a preference for branched guests rather than highly flexible, unbranched derivatives. The complexity of binding of these isomers is magnified when considering molecular differentiation between pairs of guests. In such cases, different guests demonstrated different propensities to self-sort; some self-sort exclusively, while others show very little propensity to do so. However, whereas the pool of guests reveals some general correlations between binding strength and structure, no obvious relationship between structure and degree of self-sorting was observed.
Cyclopeptides containing the DEKS motif as conformationally restricted collagen telopeptide analogues: synthesis and conformational analysis by Robert Wodtke; Gloria Ruiz-Gómez; Manuela Kuchar; M. Teresa Pisabarro; Pavlina Novotná; Marie Urbanová; Jörg Steinbach; Jens Pietzsch; Reik Löser (1878-1896).
The collagen telopeptides play an important role for lysyl oxidase-mediated crosslinking, a process which is deregulated during tumour progression. The DEKS motif which is located within the N-terminal telopeptide of the α1 chain of type I collagen has been suggested to adopt a βI-turn conformation upon docking to its triple-helical receptor domain, which seems to be critical for lysyl oxidase-catalysed deamination and subsequent crosslinking by Schiff-base formation. Herein, the design and synthesis of cyclic peptides which constrain the DEKS sequence in a β-turn conformation will be described. Lysine-side chain attachment to 2-chlorotrityl chloride-modified polystyrene resin followed by microwave-assisted solid-phase peptide synthesis and on-resin cyclisation allowed for an efficient access to head-to-tail cyclised DEKS-derived cyclic penta- and hexapeptides. An Nε-(4-fluorobenzoyl)lysine residue was included in the cyclopeptides to allow their potential radiolabelling with fluorine-18 for PET imaging of lysyl oxidase. Conformational analysis by 1H NMR and chiroptical (electronic and vibrational CD) spectroscopy together with MD simulations demonstrated that the concomitant incorporation of a d-proline and an additional lysine for potential radiolabel attachment accounts for a reliable induction of the desired βI-turn structure in the DEKS motif in both DMSO and water as solvents. The stabilised conformation of the cyclohexapeptide is further reflected by its resistance to trypsin-mediated degradation. In addition, the deaminated analogue containing allysine in place of lysine has been synthesised via the corresponding ε-hydroxynorleucine containing cyclohexapeptide. Both ε-hydroxynorleucine and allysine containing cyclic hexapeptides have been subjected to conformational analysis in the same manner as the lysine-based parent structure. Thus, both a conformationally restricted lysyl oxidase substrate and product have been synthetically accessed, which will enable their potential use for molecular imaging of these important enzymes.
E. coli cells expressing the Baeyer–Villiger monooxygenase ‘MO14’ (ro03437) from Rhodococcus jostii RHA1 catalyse the gram-scale resolution of a bicyclic ketone in a fermentor by Benjamin D. Summers; Muhiadin Omar; Thomas O. Ronson; Jared Cartwright; Michael Lloyd; Gideon Grogan (1897-1903).
The Baeyer–Villiger monooxygenase (BVMO) ‘MO14’ from Rhodococcus jostii RHA1, is an enantioselective BVMO that catalyses the resolution of the model ketone substrate bicyclo[3.2.0]hept-2-en-6-one to the (1S,5R)-2-oxa lactone and the residual (1S,5R)-substrate enantiomer. This regio-plus enantioselective behaviour is highly unusual for BVMOs, which often perform enantiodivergent biotransformations of this substrate. The scaleability of the transformation was investigated using fermentor-based experiments, in which variables including gene codon optimisation, temperature and substrate concentration were investigated. E. coli cells expressing MO14 catalysed the resolution of bicyclo[3.2.0]hept-2-en-6-one to yield (1S,5R)-2-oxa lactone of >99% ee and (1S,5R)-ketone of 96% ee after 14 h at a temperature of 16 °C and a substrate concentration of 0.5 g L−1 (4.5 mM). MO14 is thus a promising biocatalyst for the production of enantio-enriched ketones and lactones derived from the [3.2.0] platform.
Studies on the diastereoselective oxidation of 1-thio-β-d-glucopyranosides: synthesis of the usually less favoured RS sulfoxide as a single diastereoisomer by Juan Francisco Moya-López; Eleonora Elhalem; Rocío Recio; Eleuterio Álvarez; Inmaculada Fernández; Noureddine Khiar (1904-1914).
A detailed study on the diastereoselective oxidation of 1-thio-β-d-glucopyranosides is reported. It has been shown that the sense and the degree of stereochemical outcome of the oxidation are highly dependent on the substituent of the sulfur and on the protective group of the C2–OH. In the case of thioglycosides with a bulky aglycone, the mesylation of C2–OH has a significant effect on the stereochemical outcome of the oxidation, affording the usually less favoured RS sulfoxide as a single diastereoisomer. The absolute configuration of the final sulfinyl glycosides was ascertained by NMR analysis and corroborated by X-ray crystallography.
Back cover (1915-1916).