Endo Conformation Research Articles

Elucidating microRNA-34a organisation within human Argonaute-2 by dynamic nuclear polarisation-enhanced magic angle spinning NMR.

Understanding mRNA regulation by microRNA (miR) relies on the structural understanding of the RNA-induced silencing complex (RISC). Here, we elucidate the structural organisation of miR-34a, which is de-regulated in various cancers, in human Argonaute-2 (hAgo2), the effector protein in RISC. This analysis employs guanosine-specific isotopic labelling and dynamic nuclear polarisation (DNP)-enhanced Magic Angle Spinning (MAS) NMR. Homonuclear correlation experiments revealed that the non-A-form helical conformation of miR-34a increases when incorporated into hAgo2 and subsequently bound to SIRT1 mRNA compared to the free miR-34a or the free mRNA:miR duplex. The C8-C1' correlation provided a nucleotide-specific distribution of C2'- and C3'-endo sugar puckering, revealing the capture of diverse dynamic conformations upon freezing. Predominantly C3'-endo puckering was observed for the seed region, while C2'-endo conformation was found in the central region, with a mixture of both conformations elsewhere. These observations provide insights into the molecular dynamics underlying miR-mediated mRNA regulation and demonstrate that experiments conducted under cryogenic conditions, such as at 90K, can capture and reveal frozen dynamic states, using methods like DNP-enhanced MAS NMR or Cryo-ElectronMicroscopy.

Molecular structure and selective theophylline complexation by conformational change of diethyl N,N'-(1,3-phenylene)dicarbamate.

The receptor ability of diethyl N,N'-(1,3-phenylene)dicarbamate (1) to form host-guest complexes with theophylline (TEO) and caffeine (CAF) by mechanochemistry was evaluated. The formation of the 1-TEO complex (C12H16N2O4·C7H8N4O2) was preferred and involves the conformational change of one of the ethyl carbamate groups of 1 from the endo conformation to the exo conformation to allow the formation of intermolecular interactions. The formation of an N-H...O=C hydrogen bond between 1 and TEO triggers the conformational change of 1. CAF molecules are unable to form an N-H...O=C hydrogen bond with 1, making the conformational change and, therefore, the formation of the complex impossible. Conformational change and selective binding were monitored by IR spectroscopy, solid-state 13C nuclear magnetic resonance and single-crystal X-ray diffraction. The 1-TEO complex was characterized by IR spectroscopy, solid-state 13C nuclear magnetic resonance, powder X-ray diffraction and single-crystal X-ray diffraction.

The Enigma of Norbormide, a Rattus-Selective Toxicant.

Norbormide (NRB) is a Rattus-selective toxicant, which was serendipitously discovered in 1964 and formerly marketed as an eco-friendly rodenticide that was deemed harmless to non-Rattus species. However, due to inconsistent efficacy and the emergence of second-generation anticoagulants, its usage declined, with registration lapsing in 2003. NRBs' lethal action in rats entails irreversible vasoconstriction of peripheral arteries, likely inducing cardiac damage: however, the precise chain of events leading to fatality and the target organs involved remain elusive. This unique contractile effect is exclusive to rat arteries and is induced solely by the endo isomers of NRB, hinting at a specific receptor involvement. Understanding NRB's mechanism of action is crucial for developing species-selective toxicants as alternatives to the broad-spectrum ones currently in use. Recent research efforts have focused on elucidating its cellular mechanisms and sites of action using novel NRB derivatives. The key findings are as follows: NRB selectively opens the rat mitochondrial permeability transition pore, which may be a factor that contributes to its lethal effect; it inhibits rat vascular KATP channels, which potentially controls its Rattus-selective vasoconstricting activity; and it possesses intracellular binding sites in both sensitive and insensitive cells, as revealed by fluorescent derivatives. These studies have led to the development of a prodrug with enhanced pharmacokinetic and toxicological profiles, which is currently undergoing registration as a novel efficacious eco-sustainable Rattus-selective toxicant. The NRB-fluorescent derivatives also show promise as non-toxic probes for intracellular organelle labelling. This review documents in more detail these developments and their implications.

Synthesis of Nucleotides Bearing the 2'-O-Trifluoromethyl Group and Their Application in RNA Analogs Preparation.

The integration of fluorine atoms into biologically active organic compounds has proved to be a vital technique in small molecule drugs. This technique can substantially enhance crucial properties, including metabolic stability, lipophilicity, and bioavailability, often with a mere addition of a single fluorine atom or a trifluoromethyl group. Over the past few decades, this concept has also been applied in nucleic acid chemistry. A commonly employed 2'-OH substitution is the introduction of a 2'-deoxy-2'-fluoro (2'-F) group. The strong electronegativity of fluorine prompts the modified siRNA to readily adopt a C3'-endo conformation, resulting in significant advantages in terms of binding affinity. To enrich the toolbox of chemical modification of oligonucleotides, the replacement of the 2'-OH with the 2'-O-trifluoromethyl group has been developed in RNA analog synthesis. Oligodeoxynucleotides containing the 2'-O-trifluoromethyl group can greatly increase the thermal stability of DNA/RNA duplexes depending on the position and amount of the modification. Moreover, 2'-O-trifluoromethylated oligodeoxynucleotide also exhibited a slightly higher resistance to snake venom phosphodiesterase than the unmodified oligodeoxynucleotide. The 2'-O-trifluoromethylated oligonucleotides can emerge as a label to study RNA structure and function as well, or to develop DNA/RNA-based diagnostics. Hence, it is necessary to report an effective method for the synthesis, deprotection, purification, and characterization of oligonucleotides bearing a 2'-O-trifluoromethyl group. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Preparation of 6-N-benzoyl-5'-O-dimethoxytrityl-2'-O-trifluoromethyl adenosine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 2: Preparation of 4-N-acetyl-5'-O-dimethoxytrityl-2'-O-trifluoromethyl cytidine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 3: Preparation of 2-N-isobutyryl-5'-O-dimethoxytrityl-2'-O-trifluoromethyl guanine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 4: Preparation of 5'-O-dimethoxytrityl-2'-O-2-trifluoromethyl uridine 3'-(2-cyanoethyl N,N-diisopropyl) phosphoramidite Basic Protocol 5: Solid-phase synthesis of 2'-O-trifluoromethylated RNA analogs Basic Protocol 6: Deprotection and purification of 2'-O-trifluoromethyl-RNAs.

Advances in RNA Labeling with Trifluoromethyl Groups.

Fluorine labeling of ribonucleic acids (RNA) in conjunction with 19 F NMR spectroscopy has emerged as a powerful strategy for spectroscopic analysis of RNA structure and dynamics, and RNA-ligand interactions. This study presents the first syntheses of 2'-OCF3 guanosine and uridine phosphoramidites, their incorporation into oligoribonucleotides by solid-phase synthesis and a comprehensive study of their properties. NMR spectroscopic analysis showed that the 2'-OCF3 modification is associated with preferential C2'-endo conformation of the U and G ribose in single-stranded RNA. When paired to the complementary strand, slight destabilization of the duplex caused by the modification was revealed by UV melting curve analysis. Moreover, the power of the 2'-OCF3 label for NMR spectroscopy is demonstrated by dissecting RNA pseudoknot folding and its binding to a small molecule. Furthermore, the 2'-OCF3 modification has potential for applications in therapeutic oligonucleotides. To this end, three 2'-OCF3 modified siRNAs were tested in silencing of the BASP1 gene which indicated enhanced performance for one of them. Importantly, together with earlier work, the present study completes the set of 2'-OCF3 nucleoside phosphoramidites to all four standard nucleobases (A, U, C, G) and hence enables applications that utilize the favorable properties of the 2'-OCF3 group without any restrictions in placing the modification into the RNA target sequence.

In silico repurposing of CNS drugs for multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease affecting numerous people worldwide. While the relapsing subtypes of MS are to some extent treatable, the disease remains incurable leading to progressive disability. Limited efficacy of current small molecule drugs necessitates development of efficient and safe MS medications. Accordingly, drug repurposing is an invaluable strategy that recognizes new targets for known drugs especially in the field of poorly addressed therapeutic areas. Drug discovery largely depends on the identification of potential binding molecules to the intended biomolecular target(s). In this regard, current study was devoted to in silico repurposing of 263 small molecule CNS drugs to achieve superior binders to some MS-related targets. On the basis of molecular docking scores, thioxanthene and benzisothiazole-based antipsychotics could be identified as potential binders to sphingosine-1-phosphate lyase (S1PL) and cyclophilin D (CypD). Tightest interaction modes were observed for zuclopenthixol-S1PL (ΔGb -7.96kcal/mol) and lurasidone-CypD (ΔGb -8.84kcal/mol) complexes. Molecular dynamics (MD) simulations proved the appropriate and stable accommodation of top-ranked drugs inside enzyme binding sites during 100ns. Hydroxyethyl piperazine of zuclopenthixol and benzisothiazole of lurasidone flipped inside the binding pocket to interact with adjacent polar and apolar residues. Solvent accessible surface area (SASA) fluctuations confirmed the results of binding trajectory analysis and showed that non-polar hydrophobic interactions played significant roles in acquired stabilities. Our results on lurasidone binding pattern were interestingly in accordance with previous reports on X-ray structures of other norbornane maleimide derivatives as CypD inhibitors. According to this, Asn144, Phe102 and Phe155 served as important residues in providing stable binding pose of lurasidone through both exo and endo conformations. Although experimental results are necessary to be achieved, the outcomes of this study proposed the potentiality of some thioxanthene and benzisothiazole-based antipsychotics for binding to S1PL and CypD, respectively, as MS-related targets.

Solvent effect on adsorption of benzylidene oxindole to C20 nanocage: A DFT approach

AbstractIn this paper, one of the selective and potent inhibitors named (E)‐3‐benzylidene‐indoline‐2‐one (I), as against different receptor tyrosine kinase in metastasis, angiogenesis, and tumor growth, is inspected in the gas phase and in solution, at B3LYP/6‐311++G** and B3LYP/AUG‐cc‐pVTZ level of theory. A stimulating issue for this biologically active species is the effect of different media on its stability, structure, and energy gap in intermolecular [4 + 2] adsorption of I (as diene) to C20 (as dienophile) to yield (E)‐3‐benzylidene‐indoline‐2‐one[20]fullerene: Ia complex. In going from gas phase to C6H6, C2H4Cl2, EtOH, MeNO2, DMSO, and H2O solvents, individually, the optimization of complex (Ia) leads to the following: (1) The thermodynamic stability; the adsorption energy difference between liquid and gas phase (∆El–g) and dipole moment (μ) seem proportional to the dielectric constant (ε) of the scrutinized media. (2) The kinetic stability; energy difference (∆EL–H) between the frontier molecular orbitals; FMO in different media is altered in the opposite direction of ε. (3) Despite of popular belief that the endo isomer emerges thermodynamically more stable than its corresponding exo isomer, we suggest formation of kinetically more stable exo isomer because of π–π stacking among the benzyl ring and C20 nanocage. (4) The possibility of hetero [4 + 2] cycloaddition is anticipated by the lowest energy barrier of 3.8 kcal/mol probed for exo transition state (TS) in gas phase, while the highest energy barrier of 7.9 kcal/mol corresponds to the endo TS in water. (5) Due to lack of the repulsion type interaction, the exo [4 + 2] cycloaddition of unstable C20 fullerene with the scrutinized oxindole can be carried out thermally at r.t. and currently hold responsible for the origin of stereoselectivity.

Biomimics of [FeFe]-hydrogenases with a pendant amine: Diphosphine complexes [Fe2(CO)4{µ-S(CH2)nS}{κ2-(Ph2PCH2)2NR}] (n = 2, 3; R = Me, Bn) towards H2 oxidation catalysts

We report the synthesis and molecular structures of [FeFe]-ase biomimics [Fe2(CO)4{µ-S(CH2)nS}{κ2-(Ph2PCH2)2NR}] (1–4) (n = 2, 3; R = Me, Bn) and a comparative study of their protonation and redox chemistry, with the aim of assessing their activity as catalysts for H2 oxidation. They are prepared in good yields upon heating the hexacarbonyls and PCNCP ligands in toluene, a minor product of one reaction (n = 3, R = Bn) being pentacarbonyl [Fe2(CO)5(µ-pdt){Ph2PCH2N(H)Bn}] (5). Crystal structures show short Fe-Fe bonds (ca. 2.54 Å) with the diphosphine occupying basal-apical sites. Each undergoes a quasi-reversible one-electron oxidation and IR-SEC shows that this results in formation of a semi-bridging carbonyl. As has previously been observed, protonation products are solvent dependent, nitrogen being the favoured site of protonation site upon addition of one equivalent of HBF4.Et2O in d6-acetone, while hydride formation is favoured in CD2Cl2. However, the rate of N to Fe2 proton-transfer varies greatly with the nature of both the dithiolate-bridge and amine-substituent. Thus with NMe complexes (1–2) N-protonation is favoured in acetone affording a mixture of endo and exo isomers, while for NBn complexes (3–4) proton-transfer to afford the corresponding μ-hydride occurs in part (for 3 edt) or exclusively (for 4 pdt). In acetone, addition of a further equivalent of HBF4.Et2O generally does not lead to hydride formation, but in CD2Cl2 dications [Fe2(CO)4{µ-S(CH2)nS}(μ-H){κ2-(Ph2PCH2)2NHR}]2+ result, in which the diphosphine can adopt either dibasal or basal-apical positions. Proton-transfer from Fe2 to N has been previously identified as a required transformation for H2 oxidation, as has the accessibility of the all-terminal carbonyl isomer of cations [Fe2(CO)4{µ-S(CH2)nS}{κ2-(Ph2PCH2)2NR}]+. We have carried out a preliminary H2 oxidation study of 3, oxidation by Fc[BF4] in the presence of excess P(o-tolyl)3 affording [HP(o-tol)3][BF4], with a turnover of ca. 2.3 ± 0.1 mol of H2 consumed per mole of 3

Coarse-grained RNA simulations with concerted c2'/c3'-endo sugar pucker transitions.

All-atom molecular dynamic simulations are generally restricted by the time scale that can be sampled. To address this issue, various coarse-grained RNA models have been developed. These models often assume the ribose, a 5 membered ring, is fixed in only one conformation, typically the 3’-endo found in A-form helices. The models neglect the 2’-endo conformation that can be found in B-form helices and other RNA structures and is known to influence ion binding and catalytic function in addition to secondary structure propensity. Accordingly, we have developed a coarse-grained RNA force field to include transitions between the two sugar pucker states in order to accurately reproduce RNA structures and thermodynamics. To model the sugar pucker, we train a coarse-grained collective variable that distinguishes between the two states. Using this collective variable, we interpolate between two sets of force field parameters to properly reflect the structural differences between the two conformational states. The parameters of the entire model are optimized against RNA structures utilizing our contrastive divergence algorithm. Our coarse-grained RNA model opens up the opportunities to study complex RNA dynamics especially those coupled to sugar pucker transitions.

Solid-state NMR chemical shift analysis for determining the conformation of ATP bound to Na,K-ATPase in its native membrane.

Structures of membrane proteins determined by X-ray crystallography and, increasingly, by cryo-electron microscopy often fail to resolve the structural details of unstable or reactive small molecular ligands in their physiological sites. This work demonstrates that 13C chemical shifts measured by magic-angle spinning (MAS) solid-state NMR (SSNMR) provide unique information on the conformation of a labile ligand in the physiological site of a functional protein in its native membrane, by exploiting freeze-trapping to stabilise the complex. We examine the ribose conformation of ATP in a high affinity complex with Na,K-ATPase (NKA), an enzyme that rapidly hydrolyses ATP to ADP and inorganic phosphate under physiological conditions. The 13C SSNMR spectrum of the frozen complex exhibits peaks from all ATP ribose carbon sites and some adenine base carbons. Comparison of experimental chemical shifts with density functional theory (DFT) calculations of ATP in different conformations and protein environments reveals that the ATP ribose ring adopts an C3'-endo (N) conformation when bound with high affinity to NKA in the E1Na state, in contrast to the C2'-endo (S) ribose conformations of ATP bound to the E2P state and AMPPCP in the E1 complex. Additional dipolar coupling-mediated measurements of H-C-C-H torsional angles are used to eliminate possible relative orientations of the ribose and adenine rings. The utilization of chemical shifts to determine membrane protein ligand conformations has been underexploited to date and here we demonstrate this approach to be a powerful tool for resolving the fine details of ligand-protein interactions.

Improving the stability of La-exchanged zeolite Y catalysts in the vapor-phase isomerization of endo-tetrahydrodicyclopentadiene by co-feeding steam

• La 3+ exchanged zeolite Y is more effective than HY catalyst for isomerizing endo-THDCPD to its exo isomer in vapor phase. • LaY catalyst has more Brönsted acidity and more moderate acid sites than HY catalyst. • Deactivated LaY catalyst could be completely recovered after calcination in air. • Improved stability of LaY catalyst was observed in the presence of a small amount of steam. The activities of La-exchanged zeolite Y (LaNaY) catalysts were investigated and compared with that of HNaY catalyst for the vapor-phase isomerization of endo-tetrahydrodicyclopentadiene (endo-THDCPD) to exo-THDCPD. HNaY and LaNaY catalysts were characterized by means of X-ray diffraction (XRD), nitrogen adsorption, NH 3 -TPD, pyridine-adsorbed Fourier Transformation Infrared Spectroscopy (FTIR). The LaNaY catalysts with La loading of 2-5 wt% showed better catalytic performance than the HNaY catalyst. All catalysts deactivated gradually with number of run. The activity of the deactivated LaNaY catalyst could be completely recovered after calcination in air for 4 h at 550 °C. The effect of steam co-feeding on the stability of the LaNaY catalyst was investigated. The results show that the stability of the LaNaY catalyst was improved by co-feeding steam compared to those in the absence of steam, which was attributed to the replacement of adamantane adsorbed on the active sites of the catalyst by competitive adsorption of water. In the presence of 5 % steam, the effect of temperature on the stability of the LaNaY catalyst was also studied. A high and stable activity was observed at 185 °C.

Asymmetric Diels‐Alder Reaction Catalyzed by Facile Recoverable Ionically Core‐Corona Polymer Microsphere‐Immobilized MacMillan Catalyst

AbstractCore‐corona polymer microsphere having sulfonic acid moiety was successfully synthesized by the surface initiated‐atom transfer radical polymerization (SI‐ATRP) of an achiral monomer with phenyl p‐styrenesulfonate using benzyl halide‐functionalized polymer microsphere, followed by the regeneration of sulfonic acid. Ionically core‐corona polymer microsphere‐immobilized MacMillan catalyst was successfully synthesized by the neutralization reaction between core‐corona polymer microsphere having sulfonic acid moiety and chiral imidazolidinone precursor. The catalyst containing hydrophobic core and corona exhibited high catalytic activity with excellent enantioselectivity (99% ee for the exo isomer and >99% for the endo isomer) in the asymmetric Diels‐Alder reaction of trans‐cinnamaldehyde and 1,3‐cyclopentadiene. The catalyst with more than 1μm diameter could be recovered quantitatively by centrifugation and reused at least four cycles without loss of the enantioselectivity.

Computational approaches to structural properties investigation of triethylammonium- and triethanolammonium-based protic ionic liquids

• Two PILs sharing the same anion were studied, that is, TEA/MsO and TEOA/MsO. • Abilities of different computational methods to study of these PIL structures are discussed. • Effects of multiparticle interactions on the structure and binding of ions are analysed. • Interionic interactions in TEOA/MsO are stronger than in TEA/MsO. • In the mesylate-based PIL the TEOA cation is in the endo-conformation. In order to conceive nature of protic ionic liquids (PILs) and reveal how the terminal hydroxyl groups in the cation affect the liquid structure we analyse the results on quantum-chemical calculations of single ion pairs of two different PILs sharing the same mesylate anion: triethylammonium-mesylate (TEA/MsO) and triethanolammonuim-mesylate (TEOA/MsO), in combination with molecular dynamics simulations. In this study, it has been revealed that in the single TEA/MsO ion pair as well as in the bulk phase, one strong short and linear (N-)H…O(-S) hydrogen bond between cation and anion is formed. In the TEOA/MsO, formation of several hydrogen bonds involving cation’s hydrogen atoms both in the NH or OH groups is possible. In addition, whereas in a single ion pair TEOA/MsO the strongest bond is (N-)H…O(-S), in the bulk phase the bond (O-)H…O(-S) becomes the strongest. Endo conformation of the TEOA cation, being typical for its isolated state, it persists both in the ion pair and in the bulk phase. However, while in the isolated ion pair no intracationic hydrogen bonds are formed, in the bulk phase formation of these bonds is highly probable.

Solvent effect on cycloaddition of C20 nanofullerene with indoline‐2‐one, at density functional theory

AbstractThe biologically active (E)‐3‐(furan‐2‐yl)methylene‐indoline‐2‐one (I) is studied, in the gas phase, C6H6, C2H4Cl2, EtOH, MeNO2, DMSO, and H2O using the self‐consistent reaction field (SCRF)—density functional theory (DFT). This species has been used in tumor growth, metastasis, and angiogenesis. A mainly interesting issue is the solvent effect on the stability, geometry, and energy of intermolecular hetero‐Diels–Alder cycloaddition of I with C20 to yield drug delivery (Ia). By optimization of adduct (Ia) from gas phase to nonpolar and then polar solvent, the following results is obtained: (1) The trend of thermodynamic and kinetic stability and also polarity seem proportional to the dielectric constant of the used solvent and formation of the hydrogen bonding. (2) In contrast to general belief that the endo isomer appears more stable than exo isomer, here, the exo isomer appears more stable than endo isomer. (3) The exo cycloaddition can be carried out thermally at room temperature and currently hold responsible for regioselectivity. (4) The possibility of endo cycloaddition is favorable by the lowest energy barrier of 4.2 kcal/mol probed in benzene, while the highest energy barrier of 7.3 kcal/mol is estimated in water. (5) Nonbonding electrostatic interaction between the sulfur heteroatom and nanocage, as well as the π–π aromatic stacking, appears to have significant destabilizing effect on the endo isomer. (6) In going from exo transition state (TS) and endo TS to and Ia cycloadduct, the molecular electrostatic potential is changed as a function of shape, size, symmetry, and regioselectivity.

Self-correcting energy transfer Diels-Alder adduct dyes

New intramolecular donor-acceptor Diels-Alder adduct dyes were synthesized with different spacer length, which shows high intramolecular energy transfer efficiency. Pure exo and endo isomers of Diels-Alder adduct dyes were isolated and prepared. Single-crystal X-ray diffraction reveals the precise configuration of exo dye isomer, and longer Diels-Alder C–C covalent single bonds than normal single bonds. Time-resolved fluorescence measurements reveal the intramolecular energy transfer process from violet-light emitting donor to green-light emitting acceptor. A rising time of acceptor emission of donor-acceptor dye was observed when the dye donor was excited by nanosecond flash lamp. Low energy transfer dye could be self-corrected into high energy transfer dye by energy donor exchanges.

Hetero Diels–Alder cycloadduct of Anti-Tumor (E)-3-X-indoline-2-thiones with C20 fullerene as drug delivery in solution vs. gas phase: A DFT survey

Four commercially available asymmetric thioindoles including (E)-3-X-indoline-2-thiones (where X = phenyl, furan-2-yl, 1H-pyrrol-2-yl, and thiophene-2-yl, I to IV, respectively) are known as selective and potent inhibitors in contradiction of different receptors for tyrosine kinases. A specifically interesting report for these biologically active species is the effect of media on their stability and stereo-selectivity in inter-molecular cycloaddition as drug delivery involving I-IV hetero Diels–Alder (as diene) with [20]fullerene (as dienophile). Here, we have tackled this survey using the SCRF method in the gas phase, C7H8, CH2Cl2, MeOH, H2O, CH3CN and DMSO, at DFT. Stability of each solute (I-IV) and Diels–Alder cycloadducts (Ia-IVa) depends on the dielectric constant of the solvent, the possibility of the hydrogen bonding and dipole–dipole interactions. Formation of the endo isomer appears energetically less favorable due to the non-bonding electrostatic repulsions between the heteroatoms and C20 (nheteroatom ↔ πC20), also the π-π aromatic stackings among the substituted rings and C20 (πsubstituted ring ↔ πC20), which affect the stability of the transition states (TSs). Even though, the endo isomer appears thermodynamically more stable, we propose formation of the kinetically more stable exo isomer due to lack of π-π aromatic stackings. These appear completely comparable to interactions of the acyclic electron rich 1,3-dienes and dienophile C60 previously held responsible for the origin of region-selections in the exo [4 + 2] cycloadditions. Theoretical predictions are waiting for inter-molecular donor–acceptor experimental testing and verifications.

8-Furylimidazolo-2'-deoxycytidine: crystal structure, packing, atropisomerism and fluorescence.

8-Furylimidazolo-2'-deoxycytidine (furImidC), C14H14N4O5, is a fluorescent analogue of 2'-deoxycytidine, also displaying the same recognition face. As a constituent of DNA, furImidC forms extraordinarily strong silver-mediated self-pairs. Crystal structure determination revealed that furImidC adopts two types of disordered residues: the sugar unit and the furyl moiety. The disorder of the sugar residue amounts to an 87:13 split. The disorder of the furyl ring results from axial chirality at the C8-C2'' bond connecting the nucleobase to the heterocycle. The two atropisomers are present in unequal proportions [occupancies of 0.69 (2) and 0.31 (2)], and the nucleobase and the furyl moiety are coplanar. Considering the atomic sites with predominant occupancy, an anti conformation with χ= - 147.2 (7)° was found at the glycosylic bond and the 2'-deoxyribosyl moiety shows a C2'-endo (S, 2T1) conformation, with P= 160.0°. A 1H NMR-based conformational analysis of the furanose puckering revealed that the S conformation predominates also in solution. In the solid state, two neighbouring furImidC molecules are arranged in a head-to-tail fashion, but with a notable tilt of the molecules with respect to each other. Consequently, one N-H...N hydrogen bond is found for neighbouring molecules within one layer, while a second N-H...N hydrogen bond is formed to a molecule of an adjacent layer. In addition, hydrogen bonding is observed between the nucleobase and the sugar residue. A Hirshfeld surface analysis was performed to visualize the intermolecular interactions observed in the X-ray study. In addition, the fluorescence spectra of furImidC were measured in solvents of different polarity and viscosity. furImidC responds to microenvironmental changes (polarity and viscosity), which is explained by a hindered rotation of the furyl residue in solvents of high viscosity.

Silylium-Ion-Promoted Hydrosilylation of Aryl-Substituted Allenes: Interception by Cyclization of the Allyl-Cation Intermediate.

A trityl-cation-initiated, silylium-ion-promoted hydrosilylation of aryl-substituted allenes is reported. Depending on the hydrosilane-to-initiator ratio, the hydrosilylation can be intercepted by an intramolecular electrophilic aromatic substitution or a Nazarov electrocyclization of an allyl-cation intermediate in the form of its endo isomer. By this, the selective formation of either the conventional 1,2-hydrosilylation product (vinylsilane) or a cyclized product (silylated indane) can be controlled.

Experimental observations on the reductive cleavage of endo and exo 3,4-O-benzylidene fucopyranoside derivatives

Reductive cleavage of methyl 3,4-O-benzylidene-α-L-fucopyranosides with BH3·THF-TfOH and NaCNBH3-TfOH systems resulted in enhanced reaction rates and selectivity compared to BH3·THF-Bu2BOTf. With this latter system, the nature of the O-2 substituent exerted a clear control on the reactivity but practically did not affect the regioselectivity. With TfOH the direction of cleavage was determined, as expected, by the configuration of the acetal carbon atom, but slightly influenced by its competitive epimerization. Protic conditions provided higher regioselectivity in the openings of the exo isomers, affording a useful approach to the practical synthesis of 3-O-benzyl ethers.

Indium-Catalyzed Cycloisomerization of 1,6-Cyclohexenylalkynes

Efficient four- and five-step routes to access functionalized bicyclo[3.2.1]oct-2-ene and bicyclo[3.3.1]nonadiene via indium-mediated cycloisomerization of 1,6-enynes has been developed. This atom-economical catalytic process was optimized and relied on the efficiency of InCl3 leading to the preparation of functionalized bicyclic adducts in up to 99% isolated yield. The cyclization occurred on two different processes (5-exo versus 6-endo pathway) and were influenced by the substitution of the alkynyl moiety. The exo process was favored for non-substituted alkynes whereas the endo pathway was generally observed for substituted alkynes. Then, the presence of electron-withdrawing groups on the aryl substituted alkyne increased the ratio of the exo isomer. DFT calculations were performed on stability of intermediates and corroborated the intervention of InCl3.