Implicit Tandem Organic-Inorganic Hybrid Perovskite Solar Cells Based on Internal Dye Sensitization: Robotized Screening, Synthesis, Device Implementation, and Theoretical Insights.

Low-dimensional hybrid perovskite materials offer significantly improved stability as well as an extensive compositional space to explore. However, they suffer from poor photovoltaic performance as compared to the 3D perovskite materials because of poor charge-transport properties. Herein, we present the concept of internal dye-sensitized hybrid perovskite compounds involving five novel low-dimensional perovskite-type materials 1-5 incorporating triarylmethane, phenazinium and near-infrared (NIR) cyanine cationic dyes, respectively. The synthesis characterization and theoretical analysis of these compounds are presented. Theoretical calculations provide interesting insights into the effects of these dyes on the band structure of the low-dimensional anionic metal-halides and especially highlight compound 1 as a promising photovoltaic candidate. Solar cell investigation of devices based on 1 were conducted. The results show an average power conversion efficiency (PCE) of about 0.1%, which is among the highest reported for a 1D material despite the use of undoped Spiro-OMeTAD as the hole-transport material (HTM). Incident photon-to-electron efficiency (IPCE) spectra confirm the contribution of the dye to the overall photocurrent of the solar cell. Moreover, examination of solar cell devices based on the bismuth-based compound 5 resulted in PCEs in the range of 0.1%. This illustrates the potential of this concept to be exploited for lead-free photovoltaics. Finally automated robotized screening of low-dimensional hybrid perovskite materials through the screening robot PROTEUS has emerged as a powerful tool in the search for novel perovskite-like materials. Our work highlights that the use of cationic dyes could induce interesting sensitizing properties to low-dimensional metal-halide chains and may therefore provide inspiration and new design strategies for the synthesis of new lead-free photovoltaic materials.

A Multicontrolled Enamine Configurational Switch Undergoing Dynamic Constitutional Exchange.

A multiresponsive enamine-based molecular switch is presented, in which forward/backward configurational rotation around the C=C bond could be precisely controlled by the addition of an acid/base or metal ions. Fluorescence turn-on/off effects and large Stokes shifts were observed while regulating the switching process with CuII . The enamine functionality furthermore enabled double dynamic regimes, in which configurational switching could operate in conjunction with constitutional enamine exchange of the rotor part. This behavior was used to construct a prototypical dynamic covalent switch system through enamine exchange with primary amines. The dynamic exchange process could be readily turned on/off by regulating the switch status with pH.

Lipid Peroxide-Mediated Oxidative Rearrangement of the Pyrazinone Carboxamide Core of Neutrophil Elastase Inhibitor AZD9819 in Blood Plasma Samples.

This study focused on the mechanistic interpretation of ex vivo oxidation of a candidate drug in blood plasma samples. An unexpected lipid peroxide-mediated epoxidation followed by a dramatic rearrangement led to production of a five-membered oxazole derivative from the original six-membered pyrazinone-carboxamide core of a human neutrophil elastase inhibitor, 6-(1-(4-cyanophenyl)-1H-pyrazol-5-yl)-N-ethyl-5-methyl-3-oxo-4-(3-(trifluoromethyl)phenyl)-3,4-dihydropyrazine-2-carboxamide (AZD9819). The rearranged oxidation product 2-(1-(4-cyanophenyl)-1H-pyrazol-5-yl)-5-(N-ethylacetamido)-N-(3-(trifluoromethyl)phenyl)oxazole-4-carboxamide was characterized by accurate-mass tandem mass spectrometry fragmentations, by two-dimensional NMR and X-ray crystallography of an authentic standard, and by incorporation of an (18)O atom from molecular (18)O2 to the location predicted by our proposed mechanism. The lipid peroxide-mediated oxidation was demonstrated by using human low-density lipoprotein (LDL) in pH 7.4 phosphate buffer and by inhibiting the oxidation with ascorbic acid or l-glutathione, two antioxidants effective in both plasma and the LDL incubation. A nucleophilic mechanism for the epoxidation of AZD9819 by lipid hydroperoxides explains the prevention of its ex vivo oxidation by acidification of the plasma samples. The discovery of the lipid peroxide-dependent oxidation of an analyte and the means of prevention could provide valuable information for biotransformation and bioanalysis.

Oxidative ring expansion of spirocyclic oxindole derivatives.

Oxidation of the spirocyclic oxindole derivative, isamic acid 1, led to decarboxylation and ring expansion to quinazolino[4,5-b]quinazoline-6,8-dione 7 rather than, as previously believed, its isomer 6. The structure of 7 was confirmed by X-ray crystallography. Condensation of isatin (indole-2,3-dione) and 2-aminobenzamide led to the spirocyclic molecule, spiro[3H-indole-3,2'(1H)quinazoline]-2,4'(1H,3H)dione 8, which was also identified as an intermediate in the oxidation of isamic acid. Mild hydrolysis of 7 gave the 10-membered molecule 22. Isamic acid could easily be converted to N-nitrosoisamic acid, which when heated in ethanol underwent a ring expansion to a hydroximino derivative, 38, of compound 6. The structure of 38 was confirmed by X-ray crystallography.

De novo determination of the crystal structure of a large drug molecule by crystal structure prediction-based powder NMR crystallography.

The crystal structure of form 4 of the drug 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoic acid is determined using a protocol for NMR powder crystallography at natural isotopic abundance combining solid-state (1)H NMR spectroscopy, crystal structure prediction, and density functional theory chemical shift calculations. This is the first example of NMR crystal structure determination for a molecular compound of previously unknown structure, and at 422 g/mol this is the largest compound to which this method has been applied so far.

Water-in-salt electrolytes made saltier by Gemini ionic liquids for highly efficient Li-ion batteries.

The water-in-salt electrolytes have promoted aqueous Li-ion batteries to become one of the most promising candidates to overcome safety concerns/issues of traditional Li-ion batteries. A simple increase of Li-salt concentration in electrolytes can successfully expand the electrochemical stability window of aqueous electrolytes beyond 2 V. However, necessary stability improvements require an increase in complexity of the ternary electrolytes. Here, we have explored the effects of novel, Gemini-type ionic liquids (GILs) as a co-solvent systems in aqueous Li[TFSI] mixtures and investigated the transport properties of the resulting electrolytes, as well as their electrochemical performance. The devices containing pyrrolidinium-based GILs show superior cycling stability and promising specific capacity in the cells based on the commonly used electrode materials LTO (Li4Ti5O12) and LMO (LiMn2O4).

Crystal Modifications of a Cyclic Guanosine Phosphorothioate Analogue, a Drug Candidate for Retinal Neurodegenerations.

In contribution to the pharmaceutical development of cyclic guanosine monophosphorothioate analogue cGMPSA as a potential active pharmaceutical ingredient (API) for the treatment of inherited retinal degenerations (IRDs), its neutral form (cGMPSA-H) and salts of sodium (-Na), calcium (-Ca), ammonium (-NH4 ), triethylammonium (-TEA), tris(hydroxymethyl)aminomethane (-Tris), benethamine (-Bnet), and benzathine (-BZ) were prepared. Their solid-state properties were studied with differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy, and dynamic vapor sorption, and their solubilities were measured in deionized H2 O as well as aqueous HCl and NaOH buffers. A total of 21 crystal modifications of cGMPSA were found and characterized by X-ray powder diffraction. Despite their crystalline character, no API forms featured any observable melting points during thermal analyses and instead underwent exothermic decomposition at ≥163 °C. Both the vapor sorption behavior and solubility were found to differ significantly across the API forms. cGMPSA-BZ featured the lowest aqueous solubility and hygroscopicity, with 50 µg/mL and 5 % mass gain at maximum relative humidity. The synthesis and crystallization of some crystal modifications were upscaled to >10 g. Single crystal X-ray diffraction was performed which resulted in the first crystal structure determination and absolute configuration of a cyclic guanosine monophosphorothioate, confirming the RP - conformation at the phosphorus atom.

Thionations using a P4S10-pyridine complex in solvents such as acetonitrile and dimethyl sulfone.

Tetraphosphorus decasulfide (P(4)S(10)) in pyridine has been used as a thionating agent for a long period of time. The moisture-sensitive reagent has now been isolated in crystalline form, and the detailed structure has been determined by X-ray crystallography. The thionating power of this storable reagent has been studied and transferred to solvents such as acetonitrile in which it has proven to be synthetically useful and exceptionally selective. Its properties have been compared with the so-called Lawesson reagent (LR). Particularly interesting are the results from thionations at relatively high temperatures (∼165 °C) in dimethyl sulfone as solvent. Under these conditions, for instance, acridone and 3-acetylindole could quickly be transformed to the corresponding thionated derivatives. Glycylglycine similarly gave piperazinedithione. At these temperatures, LR is inefficient due to rapid decomposition. The thionated products are generally cleaner and more easy to obtain because in the crystalline reagent, impurities which invariably are present in the conventional reagents, P(4)S(10) in pyridine or LR, have been removed.

Dimensional caging of polyiodides.

Two series of iodide and polyiodide chain structures have been synthesized through the employment of secondary interactions between polycation, long-chain, hydrocarbon cations. These compounds represent examples of crystal engineering, employing a simple strategy of synthesis. The two series are related, and the capacity to incorporate polyiodide ions dependent on the length of the hydrocarbon chains is indicated.

The Oncolytic Efficacy and in Vivo Pharmacokinetics of [2-(4-Chlorophenyl)quinolin-4-yl](piperidine-2-yl)methanol (Vacquinol-1) Are Governed by Distinct Stereochemical Features.

Glioblastoma remains an incurable brain cancer. Drugs developed in the past 20 years have not improved the prognosis for patients, necessitating the development of new treatments. We have previously reported the therapeutic potential of the quinoline methanol Vacquinol-1 (1) that targets glioblastoma cells and induces cell death by catastrophic vacuolization. Compound 1 is a mixture of four stereoisomers due to the two adjacent stereogenic centers in the molecule, complicating further development in the preclinical setting. This work describes the isolation and characterization of the individual isomers of 1 and shows that these display stereospecific pharmacokinetic and pharmacodynamic features. In addition, we present a stereoselective synthesis of the active isomers, providing a basis for further development of this compound series into a novel experimental therapeutic for glioblastoma.

New high-nuclearity Ni-Pt carbonyl clusters: synthesis and X-ray structure of the ordered [HNi24Pt17(CO)46]5- and the substitutionally Ni/Pt disordered [Ni32Pt24(CO)56]6- cluster anions.

Condensation between preformed Ni-Pt and Pt carbonyl clusters leads to the new [H(6-n)Ni(24)Pt(17)(CO)(46)](n-)(n= 5, 6) and the substitutionally Ni/Pt disordered [Ni(24)(Ni(12-x)Pt(x))Pt(20)(CO)(56)](6-) (x = 4) carbonyl clusters, the latter of which represents the highest nuclearity homoleptic carbonyl cluster anion so far reported.

Metal Iodides in Polyiodide Networks: Synthesis and Structure of Binary Metal Iodide-Iodine Compounds Stable under Ambient Conditions.

The reaction between HgI(2)(C(6)N(4)H(12)) and HI in ethanol solution results in the binary metal iodide-iodine complexes [C(6)N(4)H(13)](2)(Hg(2)I(6))(1/2)(HgI(3)).(1)/(2)I(2), which are stable under ambient conditions. The structure consists of C(6)N(4)H(13)(+) cations, discrete trigonal HgI(3)(-) ions, and.Hg(2)I(6)(2)(-).I(2).Hg(2)I(6)(2)(-). chains in the crystallographic b direction, which are formed by I(2) molecules connecting the bridging iodines of the Hg(2)I(6)(2)(-) dimers. The intra- and intermolecular I-I distances of iodine in the chain are 2.7402(15) and 3.438(1) Å, respectively. The Raman spectrum of [C(6)N(4)H(13)](2)(Hg(2)I(6))(1/2)(HgI(3)).(1)/(2)I(2) confirms the interaction between the iodine molecules and Hg(2)I(6)(2)(-) ions. The structure of [NH(4)](HgI(3)).H(2)O, obtained during the synthesis of [C(6)N(4)H(13)](2)(Hg(2)I(6))(1/2)(HgI(3)).(1)/(2)I(2), is also reported. Crystal data for [C(6)N(4)H(13)](2)(Hg(2)I(6))(1/2)(HgI(3)).(1)/(2)I(2): a = 14.275(3) Å, b = 19.721(4) Å, c = 10.416(2) Å, orthorhombic space group Pbam; Z = 4. Crystal data for [NH(4)](HgI(3)).H(2)O: a = 8.7246(4) Å, b = 9.7860(3) Å, c = 11.1103(4) Å, orthorhombic space group Ama2; Z = 4.

In silico solid state perturbation for solubility improvement.

Solubility is a frequently recurring issue within pharmaceutical industry, and new methods to proactively resolve this are of fundamental importance. Here, a novel methodology is reported for intrinsic solubility improvement, using in silico prediction of crystal structures, by perturbing key interactions in the crystalline solid state. The methodology was evaluated with a set of benzodiazepine molecules, using the two-dimensional molecular structure as the only a priori input. The overall trend in intrinsic solubility was correctly predicted for the entire set of benzodiazepines molecules. The results also indicate that, in drug compound series where the melting point is relatively high (i.e., "brick dust" compounds), the reported methodology should be very suitable for identifying strategically important molecular substitutions to improve solubility. As such, this approach could be a useful predictive tool for rational compound design in the early stages of drug development.

Circumventing seizure activity in a series of G protein coupled receptor 119 (GPR119) agonists.

Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippocampal brain slice assay was used to assess the seizure liability of subsequent compounds, leading to the identification of an aryl sulfone as a replacement for the 3-cyano pyridyl group. Subsequent optimization to improve the overall profile, specifically with regard to hERG activity, led to alkyl sulfone 16. This compound did not cause tonic-clonic convulsions in mice, had a good pharmacokinetic profile, and displayed in vivo efficacy in murine models. Importantly, it was shown to be effective in wild-type (WT) but not GPR119 knockout (KO) animals, consistent with the pharmacology observed being due to agonism of GPR119.

Substituted 7-amino-5-thio-thiazolo[4,5-d]pyrimidines as potent and selective antagonists of the fractalkine receptor (CX3CR1).

We have developed two parallel series, A and B, of CX3CR1 antagonists for the treatment of multiple sclerosis. By modifying the substituents on the 7-amino-5-thio-thiazolo[4,5-d]pyrimidine core structure, we were able to achieve compounds with high selectivity for CX3CR1 over the closely related CXCR2 receptor. The structure-activity relationships showed that a leucinol moiety attached to the core-structure in the 7-position together with α-methyl branched benzyl derivatives in the 5-position displayed promising affinity, and selectivity as well as physicochemical properties, as exemplified by compounds 18a and 24h. We show the preparation of the first potent and selective orally available CX3CR1 antagonists.

Synthesis and functionalization of cyclic sulfonimidamides: a novel chiral heterocyclic carboxylic Acid bioisostere.

An efficient synthesis of aryl substituted cyclic sulfonimidamides designed as chiral nonplanar heterocyclic carboxylic acid bioisosteres is described. The cyclic sulfonimidamide ring system could be prepared in two steps from a trifluoroacetyl protected sulfinamide and methyl ester protected amino acids. By varying the amino acid, a range of different C-3 substituted sulfonimidamides could be prepared. The compounds could be further derivatized in the aryl ring using standard cross-coupling reactions to yield highly substituted cyclic sulfonimidamides in excellent yields. The physicochemical properties of the final compounds were examined and compared to those of the corresponding carboxylic acid and tetrazole derivatives. The unique nonplanar shape in combination with the relatively strong acidity (pK a 5-6) and the ease of modifying the chemical structure to fine-tune the physicochemical properties suggest that this heterocycle can be a valuable addition to the range of available carboxylic acid isosteres.

Stereocontrolled access to optically-enriched oxabispidines.

A range of chiral, optically-enriched bicyclic oxabispidines were prepared from (S)-(-)-2,3-epoxypropylphthalimide using an efficient sequence featuring a stereocontrolled intramolecular Mannich reaction as the key transformation.

Use of small-molecule crystal structures to address solubility in a novel series of G protein coupled receptor 119 agonists: optimization of a lead and in vivo evaluation.

G protein coupled receptor 119 (GPR119) is viewed as an attractive target for the treatment of type 2 diabetes and other elements of the metabolic syndrome. During a program toward discovering agonists of GPR119, we herein describe optimization of an initial lead compound, 2, into a development candidate, 42. A key challenge in this program of work was the insolubility of the lead compound. Small-molecule crystallography was utilized to understand the intermolecular interactions in the solid state and resulted in a switch from an aryl sulphone to a 3-cyanopyridyl motif. The compound was shown to be effective in wild-type but not knockout animals, confirming that the biological effects were due to GPR119 agonism.