Styryl lactone derivatives and aristolactam alkaloids from Goniothalamus tapis Miq. and their α-glucosidase inhibitory activity.

Two new styryl lactone derivatives, goniothapic acids A (1) and B (2), and 18 known compounds, were isolated from the twig and leaf extracts of Goniothalamus tapis Miq. The structures of new compounds were characterised by spectroscopic methods and HRESITOFMS. Their absolute configuration was established by comparing the experimental and calculated ECD spectra. Eleven compounds were evaluated for their α-glucosidase inhibitory activity. Of these, (-)-goniothalamin (5) and oldhamactam (16) showed the best α-glucosidase inhibitory activity with IC50 values of 54.8 and 57.9 µM, respectively.

Thorectidiol A Isolated from the Marine Sponge Dactylospongia elegans Disrupts Interactions of the SARS-CoV-2 Spike Receptor Binding Domain with the Host ACE2 Receptor.

Thorectidiols isolated from the marine sponge Dactylospongia elegans (family Thorectidae, order Dictyoceratida) collected in Papua New Guinea are a family of symmetrical and unsymmetrical dimeric biphenyl meroterpenoid stereoisomers presumed to be products of oxidative phenol coupling of a co-occurring racemic monomer, thorectidol (3). One member of the family, thorectidiol A (1), has been isolated in its natural form, and its structure has been elucidated by analysis of NMR, MS, and ECD data. Acetylation of the sponge extract facilitated isolation of additional thorectidiol diacetate stereoisomers and the isolation of the racemic monomer thorectidol acetate (6). Racemic thorectidiol A (1) showed selective inhibition of the SARS-CoV-2 spike receptor binding domain (RBD) interaction with the host ACE2 receptor with an IC50 = 1.0 ± 0.7 µM.

Three new indole diterpenoids from Aspergillus aculeatus KKU-CT2.

Three new indole diterpenoids, aculeatupenes A-C (1-3), together with four known compounds (4-7), were isolated from the mycelium of Aspergillus aculeatus KKU-CT2. Their structures were established by spectroscopic evidence and absolute configurations of 1-3 were determined by comparison of their experimental and calculated ECD spectra. Compounds 1, 2, and emindole SB (4) showed weak cytotoxicity against HelaS3, KB, HepG2, MCF-7, and A549 cancer cell lines with IC50 values in the range of 11.12-67.81 µM. Compound 3 showed weak cytotoxicity against HelaS3 cell lines with an IC50 value of 17.48 µM but non-cytotoxicity against Vero cell line. In addition, compound 1 exhibited weak antibacterial activity against Bacillus cereus.[Formula: see text].

How Long Can A C-C σ-Single Bond Be?

In a specifically designed molecular structure, two sp2-hybridized carbon atoms align their unhybridized 2pz orbitals in the same orientation to form an extremely long C2pz-C2pz σ-single bond that goes beyond 3 Å in length. This new type of C-C σ-bond (coined as a fringe bond) can be made more than 1 Å longer than the current experimental world record (∼1.8 Å) and 300 kJ/mol weaker than the ordinary C-C σ-bond (∼330 kJ/mol). If such molecular monomers are polymerized into infinite chains, the extended long C-C saturated σ-bonding framework manifests band gaps similar to those of some conventional iconic organic-conducting polymers based on conjugated networks of unsaturated bonds.

Thermal decomposition of syn- and anti-dihydropyrenes; functional group-dependent decomposition pathway.

Syn and anti dihydropyrene (DHP) are excellent thermochromes, and therefore extensively studied for their thermochromic and photochromic properties, respectively. However, they suffer from thermal decomposition due to thermal instability. In this study, we thoroughly investigated pathways for the thermal decomposition of anti- and syn- dihydropyrenes through computational methods. The decomposition pathways include sigmatropic shift and hemolytic and heterolytic (cationic and anionic) cleavages. The decomposition pathway is influenced not only by the dihydropyrene (syn- or anti-) but also by the functional groups present. For anti-dihydropyrenes, sigmatropic shift is the most plausible pathways for CN and CHO internal groups. The cascade of sigmatropic shifts is followed by elimination to deliver substituted pyrenes. For CH3- and H- dihydropyrenes, hemolytic cleavage of the internal groups is the most plausible pathway for decomposition to pyrenes. The pathway is changed to heterolytic cleavage when the internal groups on the dihydropyrenes are Cl-, Br-, and SMe-. Comparison of the activation barriers for syn (30.18 kcal mol-1) and anti (32.10 kcal mol-1) dimethyldihydropyrenes for radical pathway reveal that decomposition of syn- DHP is more facile over anti-, which is consistent with the experimental observation. The decomposition pathway for syn-dihydropyrene is also hemolytic in cleavage when the internal groups are methyl and hydrogen. Syn-dihydropyrenes (symmetrical or unsymmetrical) bearing CN group do not follow sigmatropic shift, quite contrary to the anti-dihydropyrene. The lack of tendency of the syn-dihydropyrene for sigmatropic shift is rationalized on the planarity of the scaffold. The results of the theoretical study are consistent with the experimental observations. The results here help in understanding the behavior of substituents on the dihydropyrene scaffold, which will be useful in designing new molecules with improved thermal stabilities. Graphical abstract Functional group dependent decomposition pathways of dihydropyrenes.

Biotransformation of ß-Mangostin by an Endophytic Fungus of Garcinia mangostana to Furnish Xanthenes with an Unprecedented Heterocyclic Skeleton.

Biotransformation of ß-mangostin (1) by the endophytic fungus Xylaria feejeensis GM06 afforded hexacyclic ring-fused xanthenes with an unprecedented hexacyclic heterocylic skeleton. ß-Mangostin (1) was transformed to two diastereomeric pairs of enantiomers, mangostafeejin A [(-)-2a/(+)-2b)] and mangostafeejin B [(-)-3a/(+)-3b)]. The chemical structures of the transformation products were elucidated by analysis of NMR and MS data, and the structure of mangostafeejin A [(-)-2a/(+)-2b)] was confirmed by single-crystal X-ray diffraction analysis. The absolute configurations of 3a and 3b were established on the basis of calculated and measured ECD data using the ECD spectra of 2a and 2b as models. The fungal biotransformation described herein provides an effective method to convert an abundant achiral plant natural product scaffold into new chiral heterocyclic scaffolds representing expanded chemical diversity for biological activity screening.

High-Energy Nitramine Explosives: A Design Strategy from Linear to Cyclic to Caged Molecules.

After carefully analyzing the Kamlet-Jacobs (K-J) equations and the structural traits of well-known explosives, hexahydro-1,3,5-trinitro-1,3,5-triazin (RDX), octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), and hexanitrohexaazaisowurtizitane (CL-20), diverse nitramine explosives including linear (Models IAn, IBn, and ICn), cyclic (Model IIn), and caged (Models IIIAn and IIIBn) molecules were designed by incorporating various number (n) of -CH2NNO2- structural unit and studied using the B3LYP/6-31G* and B3PW91/6-31G** methods of the density functional theory. Computational results show that all of the energetic parameters, that is, density (ρ), detonation velocity (D), and detonation pressure (P), follow the order of IIIBn > IIIAn > IIn > IAn > IBn > ICn. With the increasing n, the D and P of linear nitramines eventually keep stable. This clearly indicates that elongating the chain length (e.g., polymerization) brings little or even negative benefit in boosting the explosive properties. The oxygen balance and the K-J equation parameter ϕ both have a significant influence on the detonation properties. Caged compound IIIA2 has not only comparable energetic properties but also better sensitivity and thermal stability than CL-20.

Proton transfer in acetylacetone and its α-halo derivatives.

A two-dimensional potential energy surface was utilized to treat the proton transfer in acetylacetone (AA) and its α-halo derivatives: α-fluoro-(FAA), α-chloro-(ClAA), and α-bromo-acetylacetone (BrAA). This potential energy function, which couples O-H stretching and in-plane bending vibrations, was acquired through ab initio calculations for a fixed skeleton geometry. The resulting potential energy surfaces were then used to calculate the proton tunneling frequencies and proton transfer barrier heights. The barrier heights (the energy difference between the saddle point and the minima) calculated at the MP2/6-31G(2d,p) level of theory for proton transfers in AA, FAA, ClAA, and BrAA are 7.2, 9.4, 6.3, and 5.9 kcal mol(-1), respectively. The theoretically predicted proton transfer barrier heights exhibit excellent linear correlations with geometrical, electronic structural, and topological parameters evaluated by the atoms-in-molecule (AIM) and natural bond orbital (NBO) analyses.

Dhilirolides E-N, meroterpenoids produced in culture by the fungus Penicillium purpurogenum collected in Sri Lanka: structure elucidation, stable isotope feeding studies, and insecticidal activity.

Extracts of laboratory cultures of the fungus Penicilium purpurogenum obtained from rotting fruit of the tree Averrhoa bilimbi growing in Sri Lanka have yielded 10 new meroterpenoids, dhilirolides E-N (5-14). The structures of the new dhilirolides have been elucidated by analysis of spectroscopic data and a single-crystal X-ray diffraction analysis of dhilirolide L (12). Dhilirolides A-N (1-14) represent the four unprecedented and rearranged dhilirane, isodhilirane, 14,15-dinordhilirane, and 23,24-dinorisodhilirane meroterpenoid carbon skeletons. Stable isotope feeding studies have confirmed the meroterpenoid biogenetic origin of the dhilirolides and provided support for a proposed genesis of the new carbon skeletons. Dhilirolide L (12) showed significant feeding inhibition and sublethal developmental disruption in the cabbage looper Trichoplusia ni, an important agricultural pest, at low concentrations.

Comprehensive computational study of decamethyldizincocene formation. 2. Reaction of KH/ZnCl2 with decamethylzincocene.

Computational methods were used to study the experimental finding that forming decamethyldizincocene is more efficient when using a reducing agent (e.g., KH) and ZnCl2 as opposed to a sole ZnR2 reagant. The results show that the methyl groups of decamethylzincocene have an indirect effect on the reaction. When zincocene is used as a reactant, the reaction with KH favors the route that results in the formation of the zincate, K(+)[Zn(η(1)-C5H5)3](-). However, the path of formation for the zincate K(+)[Zn(η(1)-C5Me5)3](-) is simply not favorable kinetically or thermodynamically, so the formation of decamethyldizincocene is the only option when decamethylzincocene is used.

Sesterterpenoids isolated from a northeastern Pacific Phorbas sp.

Four new sesterterpenoids, ansellone B (4), phorbadione (5), secoepoxyansellone A (6), and alotaketal C (7), have been isolated from specimens of the sponge Phorbas sp. collected in British Columbia. Ansellone B (4) has an unprecedented heterocyclic skeleton featuring an oxocane ring, and secoepoxyansellone A (6) is the first example of the degraded "secoansellane" sesterterpenoid carbon skeleton. Alotaketal C (7) is an activator of cAMP signaling in HEK cells.

Comprehensive computational study of decamethyldizincocene formation. 1. Reaction of ZnR2 reagents with decamethylzincocene.

Computational methods were used to study the surprising 2004 synthesis of decamethyldizincocene, Zn2(η(5)-C5Me5)2, which was the first molecule to have a direct, unbridged bond between two first-row transition metals. The computational results show that the methyl groups of decamethylzincocene, Zn(η(5)-C5Me5)(η(1)-C5Me5), affect the transition-state stability of its reaction with ZnEt2 (or ZnPh2) through steric hindrance, and this could possibly allow a counter-reaction, the homolytic dissociation of Zn(η(5)-C5Me5)(η(1)-C5Me5) into Zn(η(5)-C5Me5)(•) and (η(1)-C5Me5)(•), to occur, and because no such steric hindrance occurs when zincocene, Zn(η(5)-C5H5)(η(1)-C5H5), is used as a reactant, its dissociation never occurs regardless of what ZnR2 reagent is used.

Nahuoic acid A produced by a Streptomyces sp. isolated from a marine sediment is a selective SAM-competitive inhibitor of the histone methyltransferase SETD8.

The histone lysine monomethyltransferase SETD8 is an epigenetic regulator of cell cycle progression. Nahuoic acid A (1), a polyketide produced in culture by a Streptomyces sp. obtained from a tropical marine sediment, is the first known selective SAM-competitive inhibitor of SETD8. The structure of nahuoic acid A (1) has been elucidated by chemical transformation and detailed analysis of spectroscopic data.

Communication: Linear-expansion shooting techniques for accelerating self-consistent field convergence.

Based on the corrected Hohenberg-Kohn-Sham total energy density functional [Y. A. Zhang and Y. A. Wang, J. Chem. Phys. 130, 144116 (2009)], we have developed two linear-expansion shooting techniques (LIST)- direct LIST (LISTd) and indirect LIST (LISTi), to accelerate the convergence of self-consistent field (SCF) calculations. Case studies show that overall LISTi is the most robust and efficient algorithm for accelerating SCF convergence, whereas LISTd is advantageous in the early stage of an SCF process. More importantly, LISTi outperforms Pulay's direct inversion in the iterative subspace (DIIS) [P. Pulay, J. Comput. Chem. 3, 556 (1982)] and its two recent improvements, energy-DIIS [K. N. Kudin, G. E. Scuseria, and E. Cancès, J. Chem. Phys. 116, 8255 (2002)] and augmented Roothaan-Hall energy-DIIS [X. Hu and W. Yang, J. Chem. Phys. 132, 054109 (2010)].

Theoretical calculations of hyperfine coupling constants for muoniated butyl radicals.

The hyperfine coupling constants (HFCCs) of all the butyl radicals that can be produced by muonium (Mu) addition to butene isomers (1- and 2-butene and isobutene) have been calculated, to compare with the experimental results for the muon and proton HFFCs for these radicals reported in paper II (Fleming, D. G.; et al. J. Phys. Chem. A 2011, 10.1021/jp109676b) that follows. The equilibrium geometries and HFCCs of these muoniated butyl radicals as well as their unsubstituted isotopomers were treated at both the spin-unrestricted MP2/EPR-III and B3LYP/EPR-III levels of theory. Comparisons with calculations carried out for the EPR-II basis set have also been made. All calculations were carried out in vacuo at 0 K only. A C-Mu bond elongation scheme that lengthens the equilibrium C-H bond by a factor of 1.076, on the basis of recent quantum calculations of the muon HFCCs of the ethyl radical, has been exploited to determine the vibrationally corrected muon HFCCs. The sensitivity of the results to small variations around this scale factor was also investigated. The computational methodology employed was "benchmarked" in comparisons with the ethyl radical, both with higher level calculations and with experiment. For the ß-HFCCs of interest, compared to B3LYP, the MP2 calculations agree better with higher level theories and with experiment in the case of the eclipsed C-Mu bond and are generally deemed to be more reliable in predicting the equilibrium conformations and muon HFCCs near 0 K, in the absence of environmental effects. In some cases though, the experimental results in paper II demonstrate that environmental effects enhance the muon HFCC in the solid phase, where much better agreement with the experimental muon HFCCs near 0 K is found from B3LYP than from MP2. This seemingly better level of agreement is probably fortuitous, due to error cancellations in the DFT calculations, which appear to mimic these environmental effects. For the staggered proton HFCCs of the butyl radicals exhibiting no environmental effect in paper II, the best agreement with experiment is consistently found from the B3LYP calculations, in agreement also with benchmark calculations carried out for the ethyl radical.

Isotope effects and the temperature dependences of the hyperfine coupling constants of muoniated sec-butyl radicals in condensed phases.

Reported here is the first µSR study of the muon (A(µ)) and proton (A(p)) ß-hyperfine coupling constants (Hfcc) of muoniated sec-butyl radicals, formed by muonium (Mu) addition to 1-butene and to cis- and trans-2-butene. The data are compared with in vacuo spin-unrestricted MP2 and hybrid DFT/B3YLP calculations reported in the previous paper (I), which played an important part in the interpretation of the data. The T-dependences of both the (reduced) muon, A(µ)'(T), and proton, A(p)(T), Hfcc are surprisingly well explained by a simple model, in which the calculated Hfcc from paper I at energy minima of 0 and near ±120° are thermally averaged, assuming an energy dependence given by a basic 2-fold torsional potential. Fitted torsional barriers to A(µ)'(T) from this model are similar (~3 kJ/mol) for all muoniated butyl radicals, suggesting that these are dominated by ZPE effects arising from the C−Mu bond, but for A(p)(T) exhibit wide variations depending on environment. For the cis- and trans-2-butyl radicals formed from 2-butene, A(µ)'(T) exhibits clear discontinuities at bulk butene melting points, evidence for molecular interactions enhancing these muon Hfcc in the environment of the solid state, similar to that found in earlier reports for muoniated tert-butyl. In contrast, for Mu−sec-butyl formed from 1-butene, there is no such discontinuity. The muon hfcc for the trans-2-butyl radical are seemingly very well predicted by B3LYP calculations in the solid phase, but for sec-butyl from 1-butene, showing the absence of further interactions, much better agreement is found with the MP2 calculations across the whole temperature range. Examples of large proton Hfcc near 0 K are also reported, due to eclipsed C−H bonds, in like manner to C−Mu, which then also exhibit clear discontinuities in A(p)(T) at bulk melting points. The data suggest that the good agreement found between theory and experiment from the B3LYP calculations for eclipsed bonds in the solid phase may be fortuitous. For the staggered protons of the sec-butyl radicals formed, no discontinuities are seen at all in A(p)(T), also demonstrating no further effects of molecular interactions on these particular proton Hfcc.

LISTb: a Better Direct Approach to LIST.

Following our recent paper on linear-expansion shooting techniques (LIST) [Wang, Y. A.; Yam, C. Y.; Chen, Y. K.; Chen, G. H. J. Chem. Phys.2011, 134, 241103], in which the direct approach (LISTd) and the indirect approach (LISTi) were proposed to accelerate the self-consistent field convergence, we discovered a highly simple solution to cure the linear-dependence problem of LISTd. The resultant method, LISTb, is a better direct approach to LIST and muscles similar performances to existing LIST methods. More promisingly, LISTb even outshines the best LIST method, LISTi, for systems involving transition-metal atoms.

Theoretical studies on structures, 13C NMR chemical shifts, aromaticity, and chemical reactivity of finite-length open-ended armchair single-walled carbon nanotubes.

The geometries, chemical shifts, aromaticity, and reactivity of finite-length open-ended armchair single-walled carbon nanotubes (SWCNTs) have been studied within density functional theory. The widely used model of capping hydrogen atoms at the open ends of a SWCNT changes the chemical activity of the SWCNT and destabilizes the frontier molecular orbitals. The edge pi-orbital of the open ends enhances both pi- and sigma-aromaticity of the first belt of hexagons of carbon atoms at the open ends. The effect of the open ends on the structure and chemical reactivity of the SWCNT reaches only the first several layers of the hexagons of carbon atoms. Additions of carbene and dichlorocarbene to the nanotube reveal that the open ends have higher reactivities than the inner regions.

Perturbative total energy evaluation in self-consistent field iterations: tests on molecular systems.

The corrected Hohenberg-Kohn-Sham and corrected Harris total energy functionals recently proposed [B. Zhou and Y. A. Wang, J. Chem. Phys. 128, 084101 (2008)] have been generalized to the Hartree-Fock method. We have tested the functionals on a few molecular systems and found them to be very useful in accelerating the convergence of the total energy during a self-consistent field process.

A brief computational study of decamethyldizincocene formation via diethylzinc and decamethylzincocene.

We have used density functional theory and ab initio methods to study different mechanistic possibilities for the formation of decamethyldizincocene from the reaction between decamethylzincocene and diethylzinc. Our results suggest that decamethyldizincocene could form from the combination of two pentamethylcyclopentadienylzinc radicals. More importantly, our data show that homolytic dissociation of decamethylzincocene into pentamethylcyclopentadienylzinc and pentamethylcyclopentadienyl radicals is 6.7 kcal/mol less costly than the analogous dissociation of zincocene. If such an energy difference is coupled with the fact that the activation barrier to form the half-sandwich product pentamethylcyclopentadienylethylzinc is 11.8 kcal/mol more costly than to form cyclopentadienylethylzinc, we can rationalize why dizincocene does not form experimentally.