Domino metathesis involving ROM-RCM of substituted norbornenes. Rapid access to densely functionalized tricyclic bridged and condensed ring systems

Domino metathesis involving ROM-RCM of appropriately constructed norbornene derivatives having multiple alkene chains leads to direct access of highly functionalized bridged tricyclic compounds while that of a compound having two norbornene units tethered through one carbon produces a linearly arrayed condensed tricyclic system

A new approach to A/B ring analogue of eleutherobin and sarcodictyns through a sequence of highly diastereofaceselective Diels-Alder reaction and ring opening-ring closing metathesis (RO-RCM)

An approach to the construction of A/B ring analogue of antitumour compounds eleutherobin and sarcodictyns is described. The key steps involve a highly diastereofaceselective Diels-Alder reaction of a dienophile containing a furanosugar moiety with cyclopentadiene and ring opening-ring closing metathesis of the resulting adduct

Expedient route to CDE ring system of schintrilactones through tandem ROM-RCM of a norbornene derivative

A concise synthesis of a highly functionalized tricyclic ring system representing the CDE core of nortriterpenoid schintrilactones A and B is described using a tandem ROM-RCM of a norbornene derivative

Effect of ring fusion stereochemistry on double bond geometry. Unexpected formation of nine-membered cyclic ether with E-configurated double bond through RCM

Formation of a nine-membered cyclic ether with E-configurated double bond was observed during construction of 5-9-5 tricycles through RCM of dienes. Ring fusion stereochemistry in the products oxonenes was found to have profound influence on the olefin geometry. cis-anti-cis 5-9-5 tricycle was obtained with Z-configurated olefin while cis-syn-cis 5-9-5 system was obtained with E- as well as Z-configurated double bond with the former predominating

A Synergistic Coassembly of Block Copolymer and Fluorescent Probe in Thin Film for Fine-Tuning the Block Copolymer Morphology and Luminescence Property of the Probe Molecules

Here, we investigate a synergistic coassembly of a block copolymer, polystyrene-<i>b</i>-poly­(4-vinylpyridine) (PS-<i>b</i>-P4VP), and a fluorescent probe molecule, pyrenebutyric acid (PBA), in thin film using block copolymer supramolecular assembly (SMA) strategy for a wide range of compositions tuned by varying the molar ratio (<i>r</i>) of PBA and 4VP units. The PBA molecules form supramolecules with PS-<i>b</i>-P4VP through H-bonding between the carboxylic acid group of 1-pyrenebutyric acid and pyridine ring of P4VP. For compositions <i>r</i> = 0, 0.1, 0.25, and 0.5, the SMAs exhibit cylindrical morphology, whereas for <i>r</i> = 0.75 and 1, the SMAs generate lamellar morphology. Interestingly, it has been observed that the orientation of the microdomains depends on the solvent used for annealing and can be switched reversibly on exposing the SMA films to corresponding solvent. In a nonselective solvent like chloroform, the microdomains are oriented normal to the substrate, whereas in a selective solvent like 1,4-dioxane, the microdomains are oriented parallel. The synergistic coassembly of PS-<i>b</i>-P4VP and PBA in SMAs with higher molar ratio results in a structure-within-structure pattern characterized by two length scales from phase separation of block copolymer and parallel π–π stacking of the pyrene moiety of PBA molecules inside the comb block. The photophysical properties of PBA in different SMAs of varying composition were studied both in solution and in thin film state and compared to pure PBA. The UV–vis study shows the H type of aggregation of PBA molecules inside the comb block by parallel stacking of the pyrene units, and the PBA molecules orient parallel to the substrate when the microdomains are oriented normal to the substrate. The pure PBA molecules in thin film exhibit excimer emission extensively, whereas the PBA molecules in different supramolecular assemblies exhibit emission ranging from monomer to mixture of monomer and excimer. The SMA shows more intense fluorescence emission compared to pure PBA both in solution and in thin film

Base-Displaced Intercalated Structure of the <i>N</i>‑(2′-Deoxyguanosin-8-yl)-3-aminobenzanthrone DNA Adduct

3-Nitrobenzanthrone (3-NBA), an environmental mutagen found in diesel exhaust and a suspected carcinogen, undergoes metabolic reduction followed by reaction with DNA to form aminobenzanthrone (ABA) adducts, with the major alkylation product being <i>N</i>-(2′-deoxyguanosin-8-yl)-3-aminobenzanthrone (C8-dG-ABA). Site-specific synthesis of the C8-dG-ABA adduct in the oligodeoxynucleotide 5′-d­(GTGC<u>X</u>T­GTTTGT)-3′:5′-d­(ACAAAC­ACGCAC)-3′; <u>X</u> = C8-dG-ABA adduct, including codons 272–275 of the <i>p</i>53 gene, has allowed for investigation into the structural and thermodynamic properties of this adduct. The conformation of the C8-dG-ABA adduct was determined using NMR spectroscopy and was refined using molecular dynamics (MD) calculations restrained by experimentally determined interproton distance restraints obtained from NOE experiments. The refined structure revealed that the C8-dG-ABA adduct formed a base-displaced intercalated conformation. The adducted guanine was shifted into the syn conformation about the glycosidic bond. The 5′- and 3′-neighboring base pairs remained intact. While this facilitated π-stacking interactions between the ABA moiety and neighboring bases, the thermal melting temperature (<i>T</i>_m) of the adduct-containing duplex showed a decrease of 11 °C as compared to the corresponding unmodified oligodeoxynucleotide duplex. Overall, in this sequence, the base-displaced intercalated conformation of the C8-dG-ABA lesion bears similarity to structures of other arylamine C8-dG adducts. However, in this sequence, the base-displaced intercalated conformation for the C8-dG-ABA adduct differs from the conformation of the <i>N</i>²-dG-ABA adduct reported by de los Santos and co-workers, in which it is oriented in the minor groove toward the 5′ end of the duplex, with the modified guanine remaining in the anti conformation about the glyosidic torsion angle, and the complementary base remaining within the duplex. The results are discussed in relationship to differences between the C8-dG-ABA and <i>N</i>²-dG-ABA adducts with respect to susceptibility to nucleotide excision repair (NER)

Mechanistic Basis for the Bypass of a Bulky DNA Adduct Catalyzed by a Y‑Family DNA Polymerase

1-Nitropyrene (1-NP), an environmental pollutant, induces DNA damage in vivo and is considered to be carcinogenic. The DNA adducts formed by the 1-NP metabolites stall replicative DNA polymerases but are presumably bypassed by error-prone Y-family DNA polymerases at the expense of replication fidelity and efficiency in vivo. Our running start assays confirmed that a site-specifically placed 8-(deoxyguanosin-<i>N</i>²-yl)-1-aminopyrene (dG^1,8), one of the DNA adducts derived from 1-NP, can be bypassed by <i>Sulfolobus solfataricus</i> DNA polymerase IV (Dpo4), although this representative Y-family enzyme was paused strongly by the lesion. Pre-steady-state kinetic assays were employed to determine the low nucleotide incorporation fidelity and establish a minimal kinetic mechanism for the dG^1,8 bypass by Dpo4. To reveal a structural basis for dCTP incorporation opposite dG^1,8, we solved the crystal structures of the complexes of Dpo4 and DNA containing a templating dG^1,8 lesion in the absence or presence of dCTP. The Dpo4·DNA-dG^1,8 binary structure shows that the aminopyrene moiety of the lesion stacks against the primer/template junction pair, while its dG moiety projected into the cleft between the Finger and Little Finger domains of Dpo4. In the Dpo4·DNA-dG^1,8·dCTP ternary structure, the aminopyrene moiety of the dG^1,8 lesion, is sandwiched between the nascent and junction base pairs, while its base is present in the major groove. Moreover, dCTP forms a Watson–Crick base pair with dG, two nucleotides upstream from the dG^1,8 site, creating a complex for “-2” frameshift mutation. Mechanistically, these crystal structures provide additional insight into the aforementioned minimal kinetic mechanism