Selective prebiotic formation of RNA pyrimidine and DNA purine nucleosides.

The nature of the first genetic polymer is the subject of major debate1. Although the 'RNA world' theory suggests that RNA was the first replicable information carrier of the prebiotic era-that is, prior to the dawn of life2,3-other evidence implies that life may have started with a heterogeneous nucleic acid genetic system that included both RNA and DNA4. Such a theory streamlines the eventual 'genetic takeover' of homogeneous DNA from RNA as the principal information-storage molecule, but requires a selective abiotic synthesis of both RNA and DNA building blocks in the same local primordial geochemical scenario. Here we demonstrate a high-yielding, completely stereo-, regio- and furanosyl-selective prebiotic synthesis of the purine deoxyribonucleosides: deoxyadenosine and deoxyinosine. Our synthesis uses key intermediates in the prebiotic synthesis of the canonical pyrimidine ribonucleosides (cytidine and uridine), and we show that, once generated, the pyrimidines persist throughout the synthesis of the purine deoxyribonucleosides, leading to a mixture of deoxyadenosine, deoxyinosine, cytidine and uridine. These results support the notion that purine deoxyribonucleosides and pyrimidine ribonucleosides may have coexisted before the emergence of life5.

Suppression of Dexter transfer by covalent encapsulation for efficient matrix-free narrowband deep blue hyperfluorescent OLEDs.

Hyperfluorescence shows great promise for the next generation of commercially feasible blue organic light-emitting diodes, for which eliminating the Dexter transfer to terminal emitter triplet states is key to efficiency and stability. Current devices rely on high-gap matrices to prevent Dexter transfer, which unfortunately leads to overly complex devices from a fabrication standpoint. Here we introduce a molecular design where ultranarrowband blue emitters are covalently encapsulated by insulating alkylene straps. Organic light-emitting diodes with simple emissive layers consisting of pristine thermally activated delayed fluorescence hosts doped with encapsulated terminal emitters exhibit negligible external quantum efficiency drops compared with non-doped devices, enabling a maximum external quantum efficiency of 21.5%. To explain the high efficiency in the absence of high-gap matrices, we turn to transient absorption spectroscopy. It is directly observed that Dexter transfer from a pristine thermally activated delayed fluorescence sensitizer host can be substantially reduced by an encapsulated terminal emitter, opening the door to highly efficient 'matrix-free' blue hyperfluorescence.

Steric Control of Luminescence in Phenyl-Substituted Trityl Radicals.

Triphenylmethyl (trityl) radicals have shown potential for use in organic optoelectronic applications, but the design of practical trityl structures has been limited to donor/radical charge-transfer systems due to the poor luminescence of alternant symmetry hydrocarbons. Here, we circumvent the symmetry-forbidden transition of alternant hydrocarbons via excited-state symmetry breaking in a series of phenyl-substituted tris(2,4,6-trichlorophenyl)methyl (TTM) radicals. We show that 3-fold phenyl substitution enhances the emission of the TTM radical and that steric control modulates the optical properties in these systems. Simple ortho-methylphenyl substitution boosts the photoluminescence quantum efficiency from 1% (for TTM) to 65% at a peak wavelength of 612 nm (for 2-T3TTM) in solution. In the crystalline solid state, the neat 2-T3TTM radical shows a remarkably high photoluminescence quantum efficiency of 25% for emission peaking at 706 nm. This has implications in the design of aryl-substituted radical structures where the electronic coupling of the substituents influences variables such as emission, charge transfer, and spin interaction.

Suppressing Cis/Trans 'Ring-Flipping' in Organoaluminium(III)-2-Pyridyl Dimers-Design Strategies Towards Lewis Acid Catalysts for Alkene Oligomerisation.

Owing to its high natural abundance compared to the commonly used transition (precious) metals, as well as its high Lewis acidity and ability to change oxidation state, aluminium has recently been explored as the basis for a range of single-site catalysts. This paper aims to establish the ground rules for the development of a new type of cationic alkene oligomerisation catalyst containing two Al(III) ions, with the potential to act co-operatively in stereoselective assembly. Five new dimers of the type [R2Al(2-py')]2 (R=Me, iBu; py'=substituted pyridyl group) with different substituents on the Al atoms and pyridyl rings have been synthesised. The formation of the undesired cis isomers can be suppressed by the presence of substituents on the 6-position of the pyridyl ring due to steric congestion, with DFT calculations showing that the selection of the trans isomer is thermodynamically controlled. Calculations show that demethylation of the dimers [Me2Al(2-py')]2 with Ph3C+ to the cations [{MeAl(2-py')}2(µ-Me)]+ is highly favourable and that the desired trans disposition of the 2-pyridyl ring units is influenced by steric effects. Preliminary experimental studies confirm that demethylation of [Me2Al(6-MeO-2-py)]2 can be achieved using [Ph3C][B(C6F5)4].

Short hydrogen bonds enhance nonaromatic protein-related fluorescence.

Fluorescence in biological systems is usually associated with the presence of aromatic groups. Here, by employing a combined experimental and computational approach, we show that specific hydrogen bond networks can significantly affect fluorescence. In particular, we reveal that the single amino acid L-glutamine, by undergoing a chemical transformation leading to the formation of a short hydrogen bond, displays optical properties that are significantly enhanced compared with L-glutamine itself. Ab initio molecular dynamics simulations highlight that these short hydrogen bonds prevent the appearance of a conical intersection between the excited and the ground states and thereby significantly decrease nonradiative transition probabilities. Our findings open the door to the design of new photoactive materials with biophotonic applications.

Highly Adaptive Nature of Group 15 Tris(quinolyl) Ligands─Studies with Coinage Metals.

The substitution of heavier, more metallic atoms into classical organic ligand frameworks provides an important strategy for tuning ligand properties, such as ligand bite and donor character, and is the basis for the emerging area of main-group supramolecular chemistry. In this paper, we explore two new ligands [E(2-Me-8-qy)3] [E = Sb (1), Bi (2); qy = quinolyl], allowing a fundamental comparison of their coordination behavior with classical tris(2-pyridyl) ligands of the type [E'(2-py)3] (E = a range of bridgehead atoms and groups, py = pyridyl). A range of new coordination modes to Cu+, Ag+, and Au+ is seen for 1 and 2, in the absence of steric constraints at the bridgehead and with their more remote N-donor atoms. A particular feature is the adaptive nature of these new ligands, with the ability to adjust coordination mode in response to the hard-soft character of coordinated metal ions, influenced also by the character of the bridgehead atom (Sb or Bi). These features can be seen in a comparison between [Cu2{Sb(2-Me-8-qy)3}2](PF6)2 (1·CuPF6) and [Cu{Bi(2-Me-8-qy)3}](PF6) (2·CuPF6), the first containing a dimeric cation in which 1 adopts an unprecedented intramolecular N,N,Sb-coordination mode while in the second, 2 adopts an unusual N,N,(π-)C coordination mode. In contrast, the previously reported analogous ligands [E(6-Me-2-py)3] (E = Sb, Bi; 2-py = 2-pyridyl) show a tris-chelating mode in their complexes with CuPF6, which is typical for the extensive tris(2-pyridyl) family with a range of metals. The greater polarity of the Bi-C bond in 2 results in ligand transfer reactions with Au(I). Although this reactivity is not in itself unusual, the characterization of several products by single-crystal X-ray diffraction provides snapshots of the ligand transfer reaction involved, with one of the products (the bimetallic complex [(BiCl){ClAu2(2-Me-8-qy)3}] (8)) containing a Au2Bi core in which the shortest Au → Bi donor-acceptor bond to date is observed.

Quantitative Measurement of Cooperativity in H-Bonded Networks.

Cooperative H-bonding interactions are a feature of supramolecular networks involving alcohols. A family of phenol oligomers, in which the hydroxyl groups form intramolecular H-bonds, was used to investigate this phenomenon. Chains of intramolecular H-bonds were characterized using nuclear magnetic resonance (NMR) spectroscopy in solution and X-ray crystallography in the solid state. The phenol oligomers were used to make quantitative measurements of the effects of the intramolecular interactions on the strengths of intermolecular H-bonding interactions between the H-bond donor on the end of the chain and a series of H-bond acceptors. Intramolecular H-bonding interactions in the chain increase the strength of a single intermolecular H-bond between the terminal phenol and quinuclidine by up to 14 kJ mol-1 in the n-octane solution. Although the magnitude of the effect increases with the length of the H-bonded chain, the first intramolecular H-bond has a much larger effect than subsequent interactions. H-bond cooperativity is dominated by pairwise interactions between nearest neighbors, and longer range effects are negligible. The results were used to develop a simple model for cooperativity in H-bond networks using an empirical parameter κ to quantify the sensitivity of the H-bond properties of a functional group to polarization. The value of κ measured in these systems was 0.33, which means that formation of the first H-bond increases the polarity of the next H-bond donor in the chain by 33%. The cumulative cooperative effect in longer H-bonded chains reaches an asymptotic value, which corresponds to a maximum increase in the polarity of the terminal H-bond donor of 50%.

Azoles as Auxiliaries and Intermediates in Prebiotic Nucleoside Synthesis.

4,5-Dicyanoimidazole and 2-aminothiazole are azoles that have previously been implicated in prebiotic nucleotide synthesis. The former compound is a byproduct of adenine synthesis, and the latter compound has been shown to be capable of separating C2 and C3 sugars via crystallization as their aminals. We now report that the elusive intermediate cyanoacetylene can be captured by 4,5-dicyanoimidazole and accumulated as the crystalline compound N-cyanovinyl-4,5-dicyanoimidazole, thus providing a solution to the problem of concentration of atmospherically formed cyanoacetylene. Importantly, this intermediate is a competent cyanoacetylene surrogate, reacting with ribo-aminooxazoline in formamide to give ribo-anhydrocytidine ─ an intermediate in the divergent synthesis of purine and pyrimidine nucleotides. We also report a prebiotically plausible synthesis of 2-aminothiazole and examine the mechanism of its formation. The utilization of each of these azoles enhances the prebiotic synthesis of ribonucleotides, while their syntheses comport with the cyanosulfidic scenario we have previously described.

Platform for Orthogonal N-Cysteine-Specific Protein Modification Enabled by Cyclopropenone Reagents.

Protein conjugates are valuable tools for studying biological processes or producing therapeutics, such as antibody-drug conjugates. Despite the development of several protein conjugation strategies in recent years, the ability to modify one specific amino acid residue on a protein in the presence of other reactive side chains remains a challenge. We show that monosubstituted cyclopropenone (CPO) reagents react selectively with the 1,2-aminothiol groups of N-terminal cysteine residues to give a stable 1,4-thiazepan-5-one linkage under mild, biocompatible conditions. The CPO-based reagents, all accessible from a common activated ester CPO-pentafluorophenol (CPO-PFP), allow selective modification of N-terminal cysteine-containing peptides and proteins even in the presence of internal, solvent-exposed cysteine residues. This approach enabled the preparation of a dual protein conjugate of 2×cys-GFP, containing both internal and N-terminal cysteine residues, by first modifying the N-terminal residue with a CPO-based reagent followed by modification of the internal cysteine with a traditional cysteine-modifying reagent. CPO-based reagents enabled a copper-free click reaction between two proteins, producing a dimer of a de novo protein mimic of IL2 that binds to the ß-IL2 receptor with low nanomolar affinity. Importantly, the reagents are compatible with the common reducing agent dithiothreitol (DTT), a useful property for working with proteins prone to dimerization. Finally, quantum mechanical calculations uncover the origin of selectivity for CPO-based reagents for N-terminal cysteine residues. The ability to distinguish and specifically target N-terminal cysteine residues on proteins facilitates the construction of elaborate multilabeled bioconjugates with minimal protein engineering.

Gold-Mediated Multiple Cysteine Arylation for the Construction of Highly Constrained Bicycle Peptides.

Bicycles are constrained bicyclic peptides formed through reaction of three cysteine residues within a linear sequence with a trivalent, symmetrical small molecule scaffold. Bicycles with high binding affinities to therapeutically important targets can be discovered using screening technologies such as phage display. Increasing the chemical diversity of Bicycles should improve the probability of finding hits to new targets and can be achieved by expanding the toolbox of Bicycle forming chemistries. Gold(III) S-arylation has recently been described as a method for the efficient bioconjugation of cysteine residues under conditions compatible with phage display. Herein, we explore the scope and generality of this methodology for Bicycle construction through the synthesis and evaluation of four novel tris-Gold complexes. These new scaffolds were systematically reacted with a variety of peptide sequences, varying in amino acid loop lengths. All four scaffolds proved to be capable and selective reactive partners for each peptide sequence and afforded the desired Bicycle products in 13-48% isolated yield. This work exemplifies Gold-mediated arylation as a general approach for construction of novel, highly constrained Bicycles.

New Insights into the Crystallographic Disorder in the Polymorphic Forms of Aspirin from Low-Frequency Vibrational Analysis.

Terahertz time-domain spectroscopy (THz-TDS) is applied to two polymorphs of acetylsalicylic acid (aspirin), and the experimental spectra are compared to lattice dynamical calculations using high accuracy density functional theory. The calculations confirm that forms I and II have very close energetic and thermodynamic properties and also that they show similar spectral features in the far-infrared region, reflecting the high degree of similarity in their crystal structures. Unique vibrational modes are identified for each polymorph which allow them to be distinguished using THz-TDS measurements. The observation of spectral features attributable to both polymorphic forms in a single sample, however, provides further evidence to support the hypothesis that crystalline aspirin typically comprises intergrown domains of forms I and II. Differences observed in the baseline of the measured THz-TDS spectra indicate a greater degree of structural disorder in the samples of form II. Calculated Gibbs free-energy curves show a turning point at 75 K, inferring that form II is expected to be more stable than form I above this temperature as a result of its greater vibrational entropy. The calculations do not account for any differences in configurational entropy that may arise from expected structural defects. Further computational work on these structures, such as ab initio molecular dynamics, would be very useful to further explore this perspective. Here, aspirin is a model system to show how the additional insight from the low-frequency vibrational information complements the structural data and allows for quantitative thermodynamic information of pharmaceutical polymorphs to be extracted. The methodology is directly applicable to other polymorphic systems.

The role of solvation in proton transfer reactions: implications for predicting salt/co-crystal formation using the ΔpKa rule.

The ΔpKa rule is commonly applied by chemists and crystal engineers as a guideline for the rational design of molecular salts and co-crystals. For multi-component crystals containing acid and base constituents, empirical evidence has shown that ΔpKa > 4 almost always leads to salts, ΔpKa < -1 almost always leads to co-crystals and ΔpKa between -1 and 4 can be either. This paper reviews the theoretical background of the ΔpKa rule and highlights the crucial role of solvation in determining the outcome of the potential proton transfer from acid to base. New data on the frequency of the occurrence of co-crystals and salts in multi-component crystal structures containing acid and base constituents show that the relationship between ΔpKa and the frequency of salt/co-crystal formation is influenced by the composition of the crystal. For unsolvated co-crystals/salts, containing only the principal acid and base components, the point of 50% probability for salt/co-crystal formation occurs at ΔpKa ≈ 1.4, while for hydrates of co-crystals and salts, this point is shifted to ΔpKa ≈ -0.5. For acid-base crystals with the possibility for two proton transfers, the overall frequency of occurrence of any salt (monovalent or divalent) versus a co-crystal is comparable to that of the whole data set, but the point of 50% probability for observing a monovalent salt vs. a divalent salt lies at ΔpKa,II ≈ -4.5. Hence, where two proton transfers are possible, the balance is between co-crystals and divalent salts, with monovalent salts being far less common. Finally, the overall role played by the "crystal" solvation is illustrated by the fact that acid-base complexes in the intermediate region of ΔpKa tip towards salt formation if ancillary hydrogen bonds can exist. Thus, the solvation strength of the lattice plays a key role in the stabilisation of the ions.

Synthesis of Heterometallic Zirconium Alkoxide Single-Source Precursors for Bimetallic Oxide Deposition.

Single-source precursors are ubiquitous in a number of areas of chemistry and material science due to their ease of use and wide range of potential applications. The development of new single-source precursors is essential in providing entries to new areas of chemistry. In this work, we synthesize nine new structurally related bimetallic metal-zirconium alkoxides, which can be used as single-source precursors to zirconia-based materials. Detailed analysis of the structures of these complexes provides important insights into the main factors influencing their aggregation. Investigation of the thermal decomposition of these species by TGA, PXRD, SEM, and EDS reveals that they can be used to produce bimetal oxides, such as Li2ZrO3, or a mixture of metal oxides, such as CuO and ZrO2. Significantly, these studies show that thermodynamically unstable forms of zirconia, such as the tetragonal phase, can be stabilized by metal doping, providing the promise for targeted deposition of zirconia materials for specific applications.

Single-Source Deposition of Mixed-Metal Oxide Films Containing Zirconium and 3d Transition Metals for (Photo)electrocatalytic Water Oxidation.

The fabrication of mixed-metal oxide films holds promise for the development of practical photoelectrochemical catalyst coatings but currently presents challenges in terms of homogeneity, cost, and scalability. We report a straightforward and versatile approach to produce catalytically active zirconium-based films for electrochemical and photoelectrochemical water oxidation. The mixed-metal oxide catalyst films are derived from novel single-source precursor oxide cage compounds containing Zr with first-row transition metals such as Co, Fe, and Cu. The Zr-based film doped with Co on fluorine-doped tin oxide (FTO)-coated glass exhibits the highest electrocatalytic O2 evolution performance in an alkaline medium and an operational stability above 18 h. The deposition of this film onto a BiVO4 photoanode significantly enhances its photoelectrochemical activity toward solar water oxidation, lowering the onset potential by 0.12-0.21 V vs reversible hydrogen electrode (RHE) and improving the maximum photocurrent density by ∼50% to 2.41 mA cm-2 for the CoZr-coated BiVO4 photoanodes compared to that for bare BiVO4.

Sodium Borates: Expanding the Electrolyte Selection for Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) are a promising grid-level storage technology due to the abundance and low cost of sodium. The development of new electrolytes for SIBs is imperative since it impacts battery life and capacity. Currently, sodium hexafluorophosphate (NaPF6 ) is used as the benchmark salt, but is highly hygroscopic and generates toxic HF. This work describes the synthesis of a series of sodium borate salts, with electrochemical studies revealing that Na[B(hfip)4 ]⋅DME (hfip=hexafluoroisopropyloxy, Oi PrF ) and Na[B(pp)2 ] (pp=perfluorinated pinacolato, O2 C2 (CF3 )4 ) have excellent electrochemical performance. The [B(pp)2 ]- anion also exhibits a high tolerance to air and water. Both electrolytes give more stable electrode-electrolyte interfaces than conventionally used NaPF6 , as demonstrated by impedance spectroscopy and cyclic voltammetry. Furthermore, they give greater cycling stability and comparable capacity to NaPF6 for SIBs, as shown in commercial pouch cells.

The Coordination Chemistry of the N-Donor-Substituted Phosphazanes.

Phosph(III)azanes, featuring the heterocyclobutane P2 N2 ring, have now been established as building blocks in main-group coordination and supramolecular compounds. Previous studies have largely involved their use as neutral P-donor ligands or as anionic N-donor ligands, derived from deprotonation of amido-phosphazanes [RNHP(µ-NR)]2 . The use of neutral amido-phosphazanes themselves as chelating, H-bond donors in anion receptors has also been an area of recent interest because of the ease by which the proton acidity and anion binding constants can be modulated, by the incorporation of electron-withdrawing exo- and endo-cyclic groups (R) and by the coordination of transition metals to the ring P atoms. We observed recently that the effect of P,N-chelation of metal atoms to the P atoms of cis-[(2-py)NHP(µ-Nt Bu)]2 (2-py=2-pyridyl) not only pre-organises the N-H functionality for optimum H-bonding to anions but also results in a large increase in anion binding constants, well above those for traditional organic receptors like squaramides and ureas. Here, we report a broader investigation of ligand chemistry of [(2-py)NHP(µ-t NBu)]2 (and of the new quinolyl derivative [(8-Qu)NHP(µ-Nt Bu)]2 (8-Qu=8-quinolyl). The additional N-donor functionality of the heterocyclic substituents and its position has a marked effect on the anion and metal coordination chemistry of both species, leading to novel structural behaviour and reactivity compared to unfunctionalized counterparts.

Uncovering the Hidden Landscape of Tris(4-pyridyl) Ligands: Topological Complexity Derived from the Bridgehead.

Supramolecular main group chemistry is a developing field which parallels the conventional domain of metallo-organic chemistry. Little explored building blocks in this area are main group metal-based ligands which have the appropriate donor symmetry to build desired molecular or extended arrangements. Tris(pyridyl) main group ligands (E(py)3 , E=main group metal) are potentially highly versatile building blocks since shifting the N-donor arms from the 2- to the 3-positions and 4-positions provides a very simple way of changing the ligand character from mononuclear/chelating to multidentate/metal-bridging. Here, the coordination behaviour of the first main group metal tris(4-pyridyl) ligands, E(4-py)3 (E=Sb, Bi, Ph-Sn) is explored, as well as their ability to build metal-organic frameworks (MOFs). The complicated topology of these MOFs shows a marked influence on the counter anion and on the ability of the E(4-py)3 ligands to switch coordination mode, depending on the steric and donor character of the bridgehead. This structure-directing influence of the bridgehead provides a potential building strategy for future molecular and MOF design in this area.

Molecular Encapsulation of Naphthalene Diimide (NDI) Based π-Conjugated Polymers: A Tool for Understanding Photoluminescence.

Conjugated polymers are an important class of chromophores for optoelectronic devices. Understanding and controlling their excited state properties, in particular, radiative and non-radiative recombination processes are among the greatest challenges that must be overcome. We report the synthesis and characterization of a molecularly encapsulated naphthalene diimide-based polymer, one of the most successfully used motifs, and explore its structural and optical properties. The molecular encapsulation enables a detailed understanding of the effect of interpolymer interactions. We reveal that the non-encapsulated analogue P(NDI-2OD-T) undergoes aggregation enhanced emission; an effect that is suppressed upon encapsulation due to an increasing π-interchain stacking distance. This suggests that decreasing π-stacking distances may be an attractive method to enhance the radiative properties of conjugated polymers in contrast to the current paradigm where it is viewed as a source of optical quenching.

Control of Crystal Symmetry Breaking with Halogen-Substituted Benzylammonium in Layered Hybrid Metal-Halide Perovskites.

Layered hybrid metal-halide perovskites with non-centrosymmetric crystal structure are predicted to show spin-selective band splitting from Rashba effects. Thus, fabrication of metal-halide perovskites with defined crystal symmetry is desired to control the spin-splitting in their electronic states. Here, we report the influence of halogen para-substituents on the crystal structure of benzylammonium lead iodide perovskites (4-XC6H4CH2NH3)2PbI4 (X = H, F, Cl, Br). Using X-ray diffraction and second-harmonic generation, we study structure and symmetry of single-crystal and thin-film samples. We report that introduction of a halogen atom lowers the crystal symmetry such that the chlorine- and bromine-substituted structures are non-centrosymmetric. The differences can be attributed to the nature of the intermolecular interactions between the organic molecules. We calculate electronic band structures and find good control of Rashba splittings. Our results present a facile approach to tailor hybrid layered metal halide perovskites with potential for spintronic and nonlinear optical applications.

Resolving Anharmonic Lattice Dynamics in Molecular Crystals with X-Ray Diffraction and Terahertz Spectroscopy.

Molecular crystals are increasingly being used for advanced applications, ranging from pharmaceutics to organic electronics, with their utility dictated by a combination of their three-dimensional structures and molecular dynamics-with anharmonicity in the low-frequency vibrations crucial to numerous bulk phenomena. Through the use of temperature-dependent x-ray diffraction and terahertz time-domain spectroscopy, the structures and dynamics of a pair of isomeric molecular crystals exhibiting nearly free rotation of a CF_{3} functional group at ambient conditions are fully characterized. Using a recently developed solid-state anharmonic vibrational correction, and applying it to a molecular crystal for the first time, the temperature-dependent spatial displacements of atoms along particular terahertz modes are obtained, and are found to be in excellent agreement with the experimental observations, including the assignment of a previously unexplained absorption feature in the low-frequency spectrum of one of the solids.