The photoprotection mechanism in the black-brown pigment eumelanin.

The natural black-brown pigment eumelanin protects humans from high-energy UV photons by absorbing and rapidly dissipating their energy before proteins and DNA are damaged. The extremely weak fluorescence of eumelanin points toward nonradiative relaxation on the timescale of picoseconds or shorter. However, the extreme chemical and physical complexity of eumelanin masks its photoprotection mechanism. We sought to determine the electronic and structural relaxation pathways in eumelanin using three complementary ultrafast optical spectroscopy methods: fluorescence, transient absorption, and stimulated Raman spectroscopies. We show that photoexcitation of chromophores across the UV-visible spectrum rapidly generates a distribution of visible excitation energies via ultrafast internal conversion among neighboring coupled chromophores, and then all these excitations relax on a timescale of ∼4 ps without transferring their energy to other chromophores. Moreover, these picosecond dynamics are shared by the monomeric building block, 5,6-dihydroxyindole-2-carboxylic acid. Through a series of solvent and pH-dependent measurements complemented by quantum chemical modeling, we show that these ultrafast dynamics are consistent with the partial excited-state proton transfer from the catechol hydroxy groups to the solvent. The use of this multispectroscopic approach allows the minimal functional unit in eumelanin and the role of exciton coupling and excited-state proton transfer to be determined, and ultimately reveals the mechanism of photoprotection in eumelanin. This knowledge has potential for use in the design of new soft optical components and organic sunscreens.

Triplets with a Twist: Ultrafast Intersystem Crossing in a Series of Electron Acceptor Materials Driven by Conformational Disorder.

Control over the populations of singlet and triplet excitons is key to organic semiconductor technologies. In different contexts, triplets can represent an energy loss pathway that must be managed (i.e., solar cells, light-emitting diodes, and lasers) or provide avenues to improve energy conversion (i.e., photon upconversion and multiplication systems). A key consideration in the interplay of singlet and triplet exciton populations in these systems is the rate of intersystem crossing (ISC). In this work, we design, measure, and model a series of new electron acceptor molecules and analyze them using a combination of ultrafast transient absorption and ultrafast broadband photoluminescence spectroscopies. We demonstrate that intramolecular triplet formation occurs within several hundred picoseconds in solution and is accelerated considerably in the solid state. Importantly, ISC occurs with sufficient rapidity to compete with charge formation in modern organic solar cells, implicating triplets in intrinsic exciton loss channels in addition to charge recombination. Density functional theory calculations reveal that ISC occurs in triplet excited states characterized by local deviations from orbital π-symmetry associated with rotationally flexible thiophene rings. In disordered films, structural distortions, therefore, result in significant increases in spin-orbit coupling, enabling rapid ISC. We demonstrate the generality of this proposal in an oligothiophene model system where ISC is symmetry-forbidden and show that conformational disorder introduced by the formation of a solvent glass accelerates ISC, outweighing the lower temperature and increased viscosity. This proposal sheds light on the factors responsible for facile ISC and provides a simple framework for molecular control over spin states.

Azide-Enolate Cycloaddition-Rearrangement Enables Direct α-Amination of Amides and Enelactam Synthesis from Esters.

Azide-enolate cycloaddition-rearrangements offer potential for rapid access to diverse molecular frameworks from simple precursors. We report here that investigations into the cycloadditions of ester or amide enolates with vinyl azides led to the identification of two reaction processes - direct α-amination of amides and lactams, and the synthesis of ene-γ-lactams from esters. The outcomes of these reactions depended on the fate of key vinyl triazoline intermediates generated in the initial cycloaddition step. Isolation of reaction intermediates in the ene-γ-lactam synthesis revealed the unexpected addition of two enolate equivalents, one of which is later eliminated. Computational studies further suggested an unusual reaction pathway involving direct addition of an enolate to the terminal carbon of the N-vinyl triazoline. In contrast, the α-amination of amides and lactams proceeded by rearrangement of the intermediate triazoline to give an imine, hydrolysis or reduction of which gave access to primary or secondary α-amino amides or lactams.

Azide-Enolate Cycloaddition-Rearrangement Enables Direct α-Amination of Amides and Enelactam Synthesis from Esters.

Invited for the cover of this issue are Dan Furkert, Joe Bell-Tyrer and co-workers at the University of Auckland and Victoria University of Wellington. The image depicts a tandem cycloaddition-rearrangement process delivering a diverse range of molecular frameworks from simple precursors. Read the full text of the article at 10.1002/chem.202300261.

Tuneable emission in single molecule dyads mediated by a charge transfer state.

The demand for fluorescent organic dyes across a broad range of applications has led to investigation into tuneable emission dyes. The tuneable nature of these dyes makes them desirable for applications in a variety of fields, including organic light-emitting diodes (OLEDs), optical sensing devices, and fluorescence imaging. In recent investigations, there have only been a handful of mechanisms used to tune emission. Herein, we present four novel perylene-acene dyads that undergo solvent tuneable emission, and propose a novel mechanism for this tuneability based on the presence of a charge transfer state. These dyes were shown to reach photoluminescence quantum efficiencies (PLQEs) as high as 45%, depending on the solvent, showing the ability for this mechanism to be used to access higher PLQE tuneable emission.

Exciton diffusion in amorphous organic semiconductors: Reducing simulation overheads with machine learning.

Simulations of exciton and charge hopping in amorphous organic materials involve numerous physical parameters. Each of these parameters must be computed from costly ab initio calculations before the simulation can commence, resulting in a significant computational overhead for studying exciton diffusion, especially in large and complex material datasets. While the idea of using machine learning to quickly predict these parameters has been explored previously, typical machine learning models require long training times, which ultimately contribute to simulation overheads. In this paper, we present a new machine learning architecture for building predictive models for intermolecular exciton coupling parameters. Our architecture is designed in such a way that the total training time is reduced compared to ordinary Gaussian process regression or kernel ridge regression models. Based on this architecture, we build a predictive model and use it to estimate the coupling parameters which enter into an exciton hopping simulation in amorphous pentacene. We show that this hopping simulation is able to achieve excellent predictions for exciton diffusion tensor elements and other properties as compared to a simulation using coupling parameters computed entirely from density functional theory. This result, along with the short training times afforded by our architecture, shows how machine learning can be used to reduce the high computational overheads associated with exciton and charge diffusion simulations in amorphous organic materials.

N-Vinyl Acrylamides: Versatile Heterobifunctional Electrophiles for Thiol-Thiol Bioconjugations.

Herein we report the first examples of thiol-selective heterobifunctional electrophiles, N-vinyl acrylamides, that enable efficient highly selective thiol-thiol bioconjugations and cysteine modification of peptides. We demonstrate that these new classes of thiol-selective scaffolds can readily undergo a thia-Michael addition and an orthogonal radical induced thiol-ene "click" reaction under biocompatible conditions. Furthermore, the formation of an unexpected Markovnikov N,S-acetal hydrothiolation was explained using computational studies. We also reveal that N-methylation of the N-vinyl acrylamide scaffold changes the regioselectivity of the reaction. We demonstrate that use of N-vinyl acrylamides shows promise as an efficient, mild, and exquisite cysteine-selective protocol for facile construction of fluorophore-labeled peptides and proteins and that the resultant conjugates are resistant to degradation and thiol exchange, thus significantly improving their biophysical properties.

Bioinspired Synthesis of the Furopyrazine Alkaloid Hyrtioseragamine A.

A biosynthetic hypothesis proposed herein was used to guide the total synthesis of the marine-derived alkaloid hyrtioseragamine A. In the key biomimetic step, an enedione underwent acid-mediated isomerization-cyclodehydration to form the rare furopyrazine core of the natural product. The spectroscopic data for the synthetic sample is in full agreement with that described in the isolation report.

A Projective Method for the Calculation of Excited-State Electronic Coupling: Isolating Charge Transfer/Recombination Processes in Organic Photovoltaics.

Electronic coupling between excited states is a vital parameter required to describe ultrafast energy and charge transfer processes that occur in photoresponsive organic materials. In such systems, short-range Coulombic, exchange, overlap, and configuration interaction effects must all be accounted for. Although a number of methods are available, the evaluation of coupling between arbitrary excited states remains challenging. In this contribution, a flexible and scalable method for the calculation of short-range electronic coupling between excited states is developed. Excitation- or charge-localized states are projected onto the adiabatic states of a dimeric molecular system using an efficient wave function overlap algorithm. In addition to correctly treating Coulombic, exchange, and overlap contributions, the inclusion of multistate interactions is inherent in the procedure. The method is then used to disentangle excitation energy transfer, charge transfer, and charge recombination processes in donor/acceptor systems relevant to organic photovoltaics, with a view toward the development of material design principles. Calculations were performed within single-excitation frameworks, but the scheme has the potential to be extended to multireference/higher-order excitation quantum-chemical methods.

Lamellarin Sulfates from the Pacific Tunicate Didemnum ternerratum.

Six new lamellarin sulfates (1-6) were isolated from the methanolic extract of the Pacific tunicate Didemnum ternerratum, collected from the Kingdom of Tonga. Mass spectrometric molecular networking through the GNPS platform was used to target the isolation of 1-6. Planar structures were elucidated through a combination of NMR and MS experiments. Through comparison of experimental and calculated ECD spectra, the absolute configurations of atropisomers 2-5 were determined, with their energetic barriers to racemization also determined computationally. The cytotoxicity of the compounds was tested against the human colon carcinoma cell line HCT-116, where lamellarin D-8-sulfate (5) exhibited moderate activity with an IC50 of 9.7 µM.

Self-Assembly of Chiral-at-End Diketopyrrolopyrroles: Symmetry Dependent Solution and Film Optical Activity and Photovoltaic Performance.

Chiral thiophene-diketopyrrolopyrrole derivatives have been synthesised to investigate the potential of stereochemistry and symmetry as a means of modulating properties by influencing self-assembly of these purely organic materials. In particular, derivatives of diketopyrrolopyrrole were employed because of their proven interest as dyes, especially for organic solar cells. The natural product myrtenal was used as the source of stereochemistry, introduced through a Kröhnke reaction of a thiophene-bearing pyridinium salt and diketopyrrolopyrroles were prepared through Suzuki coupling with this chiral moiety at one end only as well as at both ends. Absorption spectroscopy and electrochemistry confirmed the potential suitability of the compounds for photovoltaic devices. The nanostructures formed by the compounds have been probed with circular dichroism spectroscopy in solution and in films. It is shown that a chiral C2 symmetric molecule assembles in solution giving a strong circular dichroic signal while as a film this optical activity is nulled, whereas an asymmetric homologue is most optically active as a thin film. The X-ray crystal structure of the asymmetric compound shows a polar order of the molecules that might explain this observation. The lack of optical activity in solution is very likely a result of the high solubility of the compound. The results reaffirm the sensitivity of circular dichroism spectroscopy to inter-chromophore organisation, whereas absorption spectroscopy in the visible region reveals only slight changes to the bands. The differing order in the compounds also affects their performance in bulk heterojunction photovoltaic devices. Atomic force microscopy of the blended thin films with the fullerene derivative usually employed (PC61 BM) showed that smooth and well mixed films were achieved, with the conditions required during spin coating depending greatly on the derivative, because of their differing solubility. The apparently better performance of the symmetrical compound (although with very low efficiency) is probably a result of the alignment of the molecules inferred by the circular dichroism experiments, whereas the asymmetric compound presumably adopts a twisted supramolecular organisation.

Pyranonaphthoquinones - isolation, biology and synthesis: an update.

Covering: 2008 to 2015. A review on the isolation, biological activity and synthesis of pyranonaphthoquinone natural products from 2008-2015 is providedThis review discusses the isolation, biological activity and synthesis of pyranonaphthoquinone natural products, covering the years 2008-2015. The pyranonaphthoquinones are a group of metabolites sharing a common naphtho[2,3-c]pyran-5,10-dione ring system that have been isolated from a wide range of microorganisms, plants and insects. In addition to their synthetically challenging molecular structures, pyranonaphthoquinones exhibit a wide array of biological activity, including anti-bacterial, anti-fungal and anti-cancer properties. The therapeutic potential of these compounds has led to a dynamic interplay between total synthesis and biological evaluation.

Unexpected Direct Synthesis of N-Vinyl Amides through Vinyl Azide-Enolate [3+2] Cycloaddition.

The unexpected synthesis of industrially important N-vinyl amides directly from aldehydes and α,ß-unsaturated N-vinyl amides from esters is reported. This reaction probably proceeds through an initial [3+2] azide-enolate cycloaddition involving a vinyl azide generated in situ. A survey of the reaction scope and preliminary mechanistic findings supported by quantum computational analysis are reported, with implications for the future development of atom-efficient amide synthesis. Intriguingly, this study suggests that (cautious) reevaluation of azidoethene as a synthetic reagent may be warranted.

Synthesis of Psychrophilin E.

The first total synthesis of psychrophilin E, a potent antiproliferative cyclic tripeptide isolated from Aspergillus versicolor ZLN-60, is reported herein. Key features of the synthesis include the installation of an amide bond between the indole-nitrogen of tryptophan and an anthranilic acid residue, and a high yielding macrolactamization of the linear tripeptide to the desired macrocycle.

Total synthesis of virgatolide B via exploitation of intramolecular hydrogen bonding.

A full account of the enantioselective total synthesis of virgatolide B is reported. Key features of the synthesis include an sp(3)-sp(2) Suzuki-Miyaura cross-coupling of a ß-trifluoroboratoamide with an aryl bromide, regioselective intramolecular carboalkoxylation, and a 1,3-anti-selective Mukaiyama aldol reaction. Intramolecular hydrogen bonding governed the regioselectivity of the key spiroketalization step, affording the natural product as a single regioisomer.

New Avenues for Organic Solar Cells Using Intrinsically Charge-Generating Materials.

The molecular electron acceptor material Y6 has been a key part of the most recent surge in organic solar cell sunlight-to-electricity power conversion efficiency, which is now approaching 20%. Numerous studies have sought to understand the fundamental photophysical reasons for the exceptional performance of Y6 and its growing family of structural derivatives. Though significant uncertainty about several details remains, many have concluded that initially photogenerated excited states rapidly convert into electron-hole charge pairs in the neat material. These charge pairs are characterized by location of the electron and hole on different Y6 molecules, in contrast to the Frenkel excitons that dominate the behavior of most organic semiconductor materials. Here, we summarize the current state of knowledge regarding Y6 photophysics and the key observations that have led to it. We then link this understanding to other advances, such as the role of quadrupolar fields in donor-acceptor blends, and the importance of molecular interactions and organization in providing the structural basis for Y6's properties. Finally, we turn our attention to ways of making use of the new photophysics of Y6, and suggest molecular doping, crystal structure tuning, and electric field engineering as promising avenues for future exploration.

Synthesis and cytotoxicity of pyranonaphthoquinone natural product analogues under bioreductive conditions.

We have synthesised a focused library of derivatives of natural products containing the pyranonaphthoquinone moiety including the first report of such a scaffold with an appended tetrazole functionality. Examples include kalafungin derivatives as well as analogues of nanaomycin and eleutherin. These compounds were assessed for cytotoxic activation by breast cancer cell lines engineered to express the prototypic human one- and two-electron quinone bioreductive enzymes, NADPH: cytochrome P450 oxidoreductase (POR) and NAD(P)H: quinoneoxidoreductase 1 (NQO1; DT-diaphorase), respectively. Several compounds were observed to be cytotoxic at sub-micromolar level and a pattern of increased aerobic potency was observed in cells over expressing POR. A subset of analogues was assessed under anoxic conditions, where cytotoxicity was reduced, implicating redox cycling as a major mechanism of toxicity. The substrate specificity for reductive enzymes is relevant to the future design of bioreductive prodrugs to treat cancer.

Highly electron deficient diketopyrrolopyrroles.

The synthesis, spectroelectrochemical and structural characteristics of highly electron-accepting diketopyrrrolopyrrole (DPP) molecules with adjoining pyridinium rings is reported, along with an assessment of their toxicity, which is apparently low. The compounds show reversible electrochemistry and in one subfamily a massive increase in molar extinction coefficient upon electrochemical reduction.