Standard density functional approximations often give questionable results for odd-electron radical complexes, with the error typically attributed to self-interaction. In density corrected density functional theory (DC-DFT), certain classes of density functional theory calculations are significantly improved by using densities more accurate than the self-consistent densities. We discuss how to identify such cases, and how DC-DFT applies more generally. To illustrate, we calculate potential energy surfaces of HO·Cl(-) and HO·H2O complexes using various common approximate functionals, with and without this density correction. Commonly used approximations yield wrongly shaped surfaces and/or incorrect minima when calculated self consistently, while yielding almost identical shapes and minima when density corrected. This improvement is retained even in the presence of implicit solvent.

We decompose the energy error of any variational density functional theory calculation into a contribution due to the approximate functional and that due to the approximate density. Typically, the functional error dominates, but in many interesting situations the density-driven error dominates. Examples range from calculations of electron affinities to preferred geometries of ions and radicals in solution. In these abnormal cases, the error in density functional theory can be greatly reduced by using a more accurate density. A small orbital gap often indicates a substantial density-driven error.

The chemical examination of two undescribed marine actinobacteria has yielded three rare merosesterterpenoids, marinoterpins A-C (1-3, respectively). These compounds were isolated from the culture broth extracts of two marine-derived actinomycetes associated with the family Streptomycetaceae, (our strains were CNQ-253 and AJS-327). The structures of the new compounds were determined by extensive interpretation of 1D and 2D NMR, MS, and combined spectroscopic data. These compounds represent new chemical motifs, combining quinoline-N-oxides with a linear sesterterpenoid side chain. Additionally, consistent in all three metabolites is the rare occurrence of two five-ring ethers, which were derived from an apparent cyclization of methyl group carbons to adjacent hydroxy-bearing methylene groups in the sesterterpenoid side chain. Genome scanning of AJS-327 allowed for the identification of the marinoterpin (mrt) biosynthetic cluster, which consists of 16 open-reading frames that code for a sesterterpene pyrophosphate synthase, prenyltransferase, type II polyketide synthase, anthranilate:CoA-ligase, and several tailoring enzymes apparently responsible for installing the N-oxide and bis-tetrahydrofuran ring motifs.

The microbial metabolites known as the macrolides are some of the most successful natural products used to treat infectious and immune diseases. Describing the structures of these complex metabolites, however, is often extremely difficult due to the presence of multiple stereogenic centers inherent in this class of polyketide-derived metabolites. With the availability of genome sequence data and a better understanding of the molecular genetics of natural product biosynthesis, it is now possible to use bioinformatic approaches in tandem with spectroscopic tools to assign the full stereostructures of these complex metabolites. In our quest to discover and develop new agents for the treatment of cancer, we observed the production of a highly cytotoxic macrolide, neaumycin B, by a marine-derived actinomycete bacterium of the genus Micromonospora. Neaumycin B is a complex polycyclic macrolide possessing 19 asymmetric centers, usually requiring selective degradation, crystallization, derivatization, X-ray diffraction analysis, synthesis, or other time-consuming approaches to assign the complete stereostructure. As an alternative approach, we sequenced the genome of the producing strain and identified the neaumycin gene cluster ( neu). By integrating the known stereospecificities of biosynthetic enzymes with comprehensive NMR analysis, the full stereostructure of neaumycin B was confidently assigned. This approach exemplifies how mining gene cluster information while integrating NMR-based structure data can achieve rapid, efficient, and accurate stereostructural assignments for complex macrolides.

Marinolides A and B, two new 24- and 26-membered bacterial macrolactones, were isolated from the marine-derived actinobacterium AJS-327 and their stereostructures initially assigned by bioinformatic data analysis. Macrolactones typically possess complex stereochemistry, the assignments of which have been one of the most difficult undertakings in natural products chemistry, and in most cases, the use of X-ray diffraction methods and total synthesis have been the major methods of assigning their absolute configurations. More recently, however, it has become apparent that the integration of bioinformatic data is growing in utility to assign absolute configurations. Genome mining and bioinformatic analysis identified the 97 kb mld biosynthetic cluster harboring seven type I polyketide synthases. A detailed bioinformatic investigation of the ketoreductase and enoylreductase domains within the multimodular polyketide synthases, coupled with NMR and X-ray diffraction data, allowed for the absolute configurations of marinolides A and B to be determined. While using bioinformatics to assign the relative and absolute configurations of natural products has high potential, this method must be coupled with full NMR-based analysis to both confirm bioinformatic assignments as well as any additional modifications that occur during biosynthesis.

Ortho-quinone methides (o-QMs) are reactive intermediates in biosynthesis that give rise to a variety of intra- and intermolecular cyclization/addition products in bacteria, fungi, and plants. Herein, we report a new metabolic deviation of an o-QM intermediate in a benzylic dehydrogenation reaction that links the newly described marine bacterial natural products dihydrotetrachlorizine and tetrachlorizine. We discovered these novel dichloropyrrole-containing compounds from actinomycete strain AJS-327 that unexpectedly harbors in its genome a biosynthetic gene cluster (BGC) of striking similarity to that of chlorizidine, another marine alkaloid bearing a different carbon skeleton. Heterologous expression of the homologous flavin-dependent oxidoreductase enzymes Tcz9 and Clz9 revealed their native functions in tetrachlorizine and chlorizidine biosynthesis, respectively, supporting divergent oxidative dehydrogenation and pyrrolizine-forming reactions. Swapping these berberine bridge enzyme-like oxidoreductases, we produced cyclized and dehydrogenated analogs of tetrachlorizine and chlorizidine, including a dearomatized chlorizidine analog that stabilizes an o-QM via conjugation with a 3H-pyrrolizine ring.

In the last 10 years, organic–inorganic hybrid perovskite solar cells have achieved unprecedented advances, to the point where they now exhibit extremely high efficiency. However, long-term stability and areal scalability limitations impede the commercial application of perovskite materials, and appropriate diagnosistic tools have become necessary to evaluate perovskite materials. Characterization of perovskite materials is regularly misinterpretated, due to unique intrinsic and extrinsic factors: degradation from the measurement source, ion migration, phase transition, and separation. Herein, studies on perovskites are reviewed that have used advanced characterization tools to overcome characterization challenges. Cryogenic temperature assisted measurements mitigate degradation or phase transitions induced by the measurement source. In situ measurements can track the variation of perovskite materials depending on external stimuli. Spatial material properties are able to be evaluated by the use of multidimensional mapping techniques. An overview of these advanced characterization tools that can overcome the challenges associated with established tools provides the opportunity for further understanding perovskite materials and solving the remaining challenges on the road to commercialization.

A new cytotoxic thiodepsipeptide, verrucosamide (1), was isolated along with the known, related cyclic peptide thiocoraline, from the extract of a marine-derived actinomycete, a Verrucosispora sp., our strain CNX-026. The new peptide, which is composed of two rare seven-membered 1,4-thiazepane rings, was elucidated by a combination of spectral methods and the absolute configuration was determined by a single X-ray diffraction study. Verrucosamide (1) showed moderate cytotoxicity and selectivity in the NCI 60 cell line bioassay. The most susceptible cell lines were MDA-MB-468 breast carcinoma with an LD50 of 1.26 µM, and COLO 205 colon adenocarcinoma with an LD50 of 1.4 µM. Also isolated along with verrucosamide were three small 3-hydroxy(alkoxy)-quinaldic acid derivatives that appear to be products of the same biosynthetic pathway.

For commercialization of perovskite solar cells (PSCs), it is important to substitute the alternative electrode for Au to decrease the unit cost. From the early stage, Ag exhibits a potential to be a good counter electrode in PSCs; however, there is an abnormal s-shaped J-V curve with the Ag electrode, and it is recovered as time passes. The perception of the aging-induced recovery process and refutation of the raised stability issues are required for commercial application of Ag electrodes. Herein, we compared the aging effect of PSCs with Ag and Au electrodes and found that only devices with Ag electrodes have a dramatical aging-induced recovery process. We observed the change of photoelectronic properties only in the devices with Ag electrodes as time passes, which mainly contributes to recovery of the s-shaped J-V curve. We verified the work function change of an aged Ag electrode and its mechanism by photoelectron spectroscopy analysis. By comparing the light stability under 1 sun intensity illumination, we can assure the practical stability of Ag electrodes in case of being encapsulated. This work suggests the profound understanding of the aging-induced recovery process of PSCs and the possibility of commercial application of Ag electrodes.