Highly Substituted 10-RO-(hetero)acenes-Electric Properties of Vacuum-Deposited Molecular Films.

The functionalization of the aromatic backbone allows the improvement of the electrical properties of acene molecules in the amorphous layered structures of organic thin films. In the present work, we discuss the electric properties of the stable, amorphous, vacuum-deposited films prepared from five highly substituted 10-RO-acenes of various electronic properties, i.e., two extreme electron-donor (1,3-dioxa-cyclopenta[b]) anthracenes with all RO substituents, two anthracene carbaldehydes and one benzo[b]carbazole carbaldehyde possessing both electron-donor and acceptor substituents. The hole mobility data were obtained using subsequent steady state space charge limited currents (SCLC) and Time of Flight (TOF) measurements, performed on the same sample and these were then compared with the results of theoretical hole mobility calculations obtained using the Density Functional Theory (DFT) quantum-chemical calculations using the Marcus-Hush theory. The study shows a good agreement between the theoretical and experimental values which allows for the quick and quantitative estimation of Einstein's mobility values for highly substituted 10-RO anthracene and benzo[b]carbazole based on chemical calculations. This agreement also proves that the transport of holes follows the hopping mechanism. The theoretical calculations indicate that the reorganization energy plays a decisive role in the transport of holes in the amorphous layers of highly substituted hetero(acenes).

Can Pharmaceutical Excipients Threaten the Aquatic Environment? A Risk Assessment Based on the Microtox® Biotest.

The ecotoxicological impact of pharmaceuticals has received considerable attention, primarily focusing on active pharmaceutical ingredients (APIs) while largely neglecting the potential hazards posed by pharmaceutical excipients. Therefore, we analyzed the ecotoxicity of 16 commonly used pharmaceutical excipients, as well as 26 API-excipient and excipient-excipient mixtures utilizing the Microtox® test. In this way, we assessed the potential risks that pharmaceutical excipients, generally considered safe, might pose to the aquatic environment. We investigated both their individual ecotoxicity and their interactions with tablet ingredients using concentration addition (CA) and independent action (IA) models to shed light on the often-overlooked ecotoxicological consequences of these substances. The CA model gave a more accurate prediction of toxicity and should be recommended for modeling the toxicity of combinations of drugs with different effects. A challenge when studying the ecotoxicological impact of some pharmaceutical excipients is their poor water solubility, which hinders the use of standard aquatic ecotoxicity testing techniques. Therefore, we used a modification of the Microtox® Basic Solid Phase protocol developed for poorly soluble substances. The results obtained suggest the high toxicity of some excipients, i.e., SLS and meglumine, and confirm the occurrence of interactions between APIs and excipients. Through this research, we hope to foster a better understanding of the ecological impact of pharmaceutical excipients, prompting the development of risk assessment strategies within the pharmaceutical industry.

Organosulfur Materials with High Photo- and Photo-Oxidation Stability: 10-Anthryl Sulfoxides and Sulfones and Their Photophysical Properties Dependent on the Sulfur Oxidation State.

While few studies show only symmetrical and poorly mono-SOn (n = 0-2) substituted acenes, in this study, we present a synthesis of a new group of unsymmetrical, significantly substituted derivatives, which revealed unique photophysical properties. Both sulfides (S), sulfoxides (SO) and sulfones (SO2) showed very high photochemical stabilities, unusual for these groups, during UV-irradiation at 254/365 nm (air O2 and Ar), which was higher than any found in the literature. For the (S)/(SO) series (254 nm), the stabilities of 80-519 min. (air O2 and Ar) were found. At 365 nm, stabilities of 124-812 min./(air O2) for (S)/(SO) and higher for (SO2) were observed. Photoluminescence lifetimes of (SOn) of the lower anthryl symmetry remained in the following order: (SO2) < (S) < (SO); those with full symmetry were in the following order: (S) < (SO) < (SO2). The enhanced photostability was explained with DFT/MS/Hammett's constants, which showed the leading role of the SOn groups in stabilization of HOMO/LUMO frontier orbitals. The SOn (n = 0-2) substituted acenes turned out to be tunable violet/blue/green emitters by oxidation of S atoms and the introduction of rich substitution.

Role of Hydrogen Bonds in Formation of Co-amorphous Valsartan/Nicotinamide Compositions of High Solubility and Durability with Anti-hypertension and Anti-COVID-19 Potential.

Physicochemical properties, in particular solubility and the associated bioavailability, are key factors in determining efficacy of poorly water-soluble drugs, which constitute 40% of new drugs in the market, and improving them is an important challenge for modern pharmacy. A recent strategy to achieve this goal is formation of stable co-amorphous solid dispersions with co-formers of low molecular weight. Here, the amorphization strategy was applied for low-soluble anti-hypertensive valsartan (VAL), an angiotensin II receptor blocker, and nicotinamide, which exhibits lung- and cardio-protective effects. Through interactions with the renin-angiotensin-aldosteron system, VAL may be used to treat both hypertension and the current pandemic coronavirus SARS-CoV-2 infection. Using mechanochemical and liquid- and solid-state approaches, solvated co-amorphous solid dispersions of VAL with nicotinamide were obtained. They were characterized by spectroscopic, thermal, and X-ray analyses. The density functional theory, quantum theory of atoms in molecules, and non-covalent interaction index calculations revealed the presence of two types of hydrogen bonds between VAL and NIC (i.e., N-H···O and O-H···O). One of them had a partially covalent character, which caused conformational changes in the flexible VAL molecule, restricting contribution of the tetrazolyl N-H donor and thus limiting the possibility of co-crystal formation. The recognized VAL/NIC1- and VAL/NIC2-type heterodimeric interactions were responsible for the excellent durability of the solid compositions and up to 24-fold better solubility than VAL alone. The synthesized dispersions constitute a new class of dually acting drugs, containing an active pharmaceutical ingredient (VAL) and supporting nutraceutical (nicotinamide).

Modification of the Microtox® Basic Solid Phase Test: A new application for the ecotoxicological studies on poorly soluble antihypertensive drugs.

Increasing consumption of angiotensin II receptor blockers (ARBs: valsartan, losartan potassium, telmisartan) is inevitably associated with their appearance in the environment and impact on aquatic and terrestrial organisms. Since the pharmaceuticals do not occur as pure substances in the environment, but as complex mixtures with other active pharmaceutical ingredients (APIs) and excipients used in pharmaceutical formulations, we compared the ecotoxicity of ARBs in various forms: as pure APIs, in pharmaceutical formulations and in mixtures with hydrochlorothiazide (HCT). Because the studied APIs are poorly water-soluble, the Microtox® Basic Solid Phase Test, utilizing bacteria Aliivibrio fischeri, has been modified by using a neutral matrix. Thus, this test, which is correlated with other tests for higher aquatic organisms, may be applied for the ecotoxicological evaluation of poorly soluble APIs. This is the first study reflecting the real situation in the environment, where non-target species are exposed to the pharmaceuticals, which can be dissolved/suspended in the liquid medium or adsorbed on the solid matrix. The results obtained indicate that the excipients are not inert substances and their presence in the environment may cause an increased risk to non-target organisms. Moreover, antagonistic effects were observed for two-component drug-drug (ARBs-HCT) mixtures.

Ecotoxicity of ammonium chlorophenoxyacetate derivatives towards aquatic organisms: Unexpected enhanced toxicity upon oxygen by sulfur replacement.

Phenoxyacetate herbicides, such as 2,4-D and MCPA, having a high toxicity to non-target organisms are commonly used for controlling broadleaf weeds in agriculture. However, novel and environmentally friendly analogs are constantly sought after. For this purpose, various substituents at the phenyl group have been tested to find the optimal balance between the potent herbicidal activity and safety for non-target species. In this work, we investigated the influence of the oxygen by sulfur replacement in the phenoxy moiety of ammonium chlorophenoxyacetates on the toxicity towards aquatic organisms, such as bacteria (Vibrio fischeri), water flea (Daphnia magna) and freshwater fish (Pimephales promelas) by determining experimental (Microtox® test - V. fischeri) and predicted (ACD Lab Percepta software - D. magna, P. promelas) EC50/LC50 values. The achieved results showed that in contrary to the literature observations, where O-compounds were more toxic than their S-analogs (urea/thiourea), the O/S replacement in chlorophenoxyacetate significantly increased ecotoxicity of the S-analogs (up to 11 times). Moreover, one- and two-substituted phenoxyacetates in the form of ammonium salts were less toxic to V. fischeri than the commercially available phenoxy herbicides in the acid form. The logP/logD values were also calculated to understand hydro/lipophilic nature of the investigated compounds and differences in their toxicity.

Mono-Aryl/Alkylthio-Substituted (Hetero)acenes of Exceptional Thermal and Photochemical Stability by the Thio-Friedel-Crafts/Bradsher Cyclization Reaction.

The highly substituted mono-aryl/alkylthio-(hetero)acenes prepared in this study have been found to be thermally more stable (Tdecomp. =331-354 °C) than the known di-aryl/alkylthio-substituted acenes by an average of 25 °C. They are also much more photostable at 254 and 365 nm (in both argon and air) than the parent anthracene and other reported anthracenes. The most photostable aryl/alkylthio-anthracenes at 254 nm were found to be 60-70 (in air) and 130 (in argon) times more stable in solution than the unsubstituted anthracene, and much more stable than known EDG/EWG-substituted anthracenes (EDG=electron-donating group, EWG=electron-withdrawing group) with an extended aromatic core. Furthermore, the acenes showed significantly higher photostability at 365 nm in both air and argon. The anthracenes were obtained by the novel thio-Friedel-Crafts/Bradsher cyclization reaction of hitherto unknown [o-(1,3-dithian-2-yl)aryl](aryl)methyl thioethers. The developed approach provides a general access to mono-aryl/alkylthio-substituted (hetero)acene frameworks containing at least three fused (hetero)aromatic rings. The characteristic feature of this approach, which leads to highly substituted acenes, is that the substituents, unlike in other methods, may be introduced at an early stage of the synthesis. DFT and TD-DFT calculations confirmed the stabilizing role of the aryl/alkylthio substituent in the mono-aryl/alkylthio-substituted anthracenes, which are the most stable anthracenes prepared to date. Their high photostability is mainly due to the quenching of singlet oxygen by the acene and the quenching of the acene S1 state by molecular oxygen.

Ammonium haloacetates - An alternative to glyphosate?

This study shows the design, synthesis and evaluation of eco(phyto)toxic and herbicidal activities of quaternary ammonium salts (QASs), derived from haloacetic acids, in context of the search for safer alternatives to the commonly used herbicide, N-(phosphonomethyl)glycine (glyphosate). The structure of the investigated QASs refers to the heteroatom sequence in the anion of glyphosate in which the (P-C)-N nitrogen atom was replaced by one or more halogens (F, Cl). The ecotoxicity of the synthesized QASs was tested against luminescent marine bacteria Vibrio fischeri (Microtox® test) and the crustaceans Heterocypris incongruens (Ostracodtoxkit F™). The phytotoxic effect of QASs was also studied with respect to spring barley (Hordeum vulgare) and common radish (Raphanus sativus L. radicula Pers.), whereas herbicidal activity was investigated in relation to popular weeds species gallant soldier (Galinsoga parviflora Cav.) and common sorrel (Rumex acetosa L.). The results showed that toxicity of the synthesized QASs depends on a number of halo-substituents, especially for bioluminescent bacteria Vibrio fischeri for which EC50 values were those varying the most. Phytotoxicity tests proved that the investigated QASs had a similar high, toxic effect both on monocotyledonous and dicotyledonous plants with exception of DIPA - DCA. Moreover, their herbicidal activity against common sorrel was comparable to glyphosate.

Total synthesis of (±)-epithuriferic acid methyl ester via Diels-Alder reaction.

In this paper, we have described the first total synthesis of (±)-epithuriferic acid methyl ester from non-natural sources, in four steps (20% overall yield). The key step involves the Diels-Alder reaction of isobenzofuran with methyl 3-(dimethoxyphosphoryl)acrylate which is controlled by "ortho" regio- and endo stereoselectivities due to the COOMe group.

Synthesis and optoelectronic properties of hexahydroxylated 10-O-R-substituted anthracenes via a new modification of the Friedel-Crafts reaction using O-protected ortho-acetal diarylmethanols.

A new modification of the Friedel-Crafts type intramolecular cyclization involving O-protected ortho-acetal diarylmethanols as a new type of reactant, was carried out for the first time in a medium containing a large amount of water at room temperature and enabled synthesis of a series of electron-rich, hexahydroxylated 10-O-R-substituted anthracenes, where R is an alkyl (Me, nBu, n-C(16)H(33)) or arylalkyl group (CH(2)Ph, CH(2)-2-Napht, CH(2)C(6)H(4)CH(2)OAr) and also evaluation of their electronic and optoelectronic properties in solution, crystal, and solid thin film. In this transformation, a central 10-O-R-substituted benzene ring was formed, fused to rings originating from two independent aromatic aldehydes. The reaction proceeded via two identified mechanisms involving acetal and/or free aldehyde groups. The acid sensitive acetal and dibenzyl alkoxy functions have never been used together in the intramolecular Friedel-Crafts type cyclization. The new compounds revealed deep blue fluorescence and quantum yields in solution around 0.3. The electrical properties investigated for thin films obtained by vacuum deposition on glass were 10-O-R-substituent dependent and showed much faster transient current decay in the case of the 10-O-CH(2)Ph derivative than for the material with a 10-O-Me substituent (the lifetime of charge carriers was 25 times shorter in this case). The AFM images of thin films, Stokes shifts, and X-ray analysis of π-stacking interactions in crystals of the new materials have been also obtained.

1-(Thiophen-3-yl)ethanone.

The structure of the title compound, C(6)H(6)OS, exhibits a flip-type disorder of the thiophene ring [occupancy ratio = 0.848 (3):0.152 (3)], which is typical for many thiophene derivatives. The puckered thiophene ring is essentially coplanar with the plane formed by the non-H atoms of the acetyl substituent, similar to its simple analogues, i.e. 3-acetyl-2-carboxythiophene, 4-acetyl-3-carboxythiophene and 3,5-diacetyl-2-ethylamino-4-methylthiophene. In the crystal structure, molecules are connected by C-H···π hydrogen bonds, forming a sheet parallel to the (001) plane. Moreover, an inspection of the crystal lattice reveals that there are short S···O contacts connecting the molecules of adjacent sheets. Comparison of the title crystal structure with its simple 3-methoxythiophene analogue shows a close similarity in the herringbone arrangement of molecules and in the presence of C-H···π interactions and S···O contacts.

La4.27Mg2.89Zn30, a new structure type with strong positional disorder.

Ternary tetralanthanum trimagnesium tricontazinc, La(4.27)Mg(2.89)Zn(30), crystallizes as a new structure type. It belongs to the structural family that may be derived from the hexagonal CaCu(5) and Th(2)Ni(17) structure types by combination of internal deformation and multiple substitution. The triangular 3(6) and hexagonal 6(3) nets are alternately stacked with Kagomé 3636 nets. The atoms with the largest radius (La) are enclosed in 18-vertex polyhedra (distorted pseudo-Frank-Kasper polyhedra). The coordination polyhedra of the two Mg atoms are bicapped and monocapped hexagonal antiprisms, with coordination numbers of 14 and 13, respectively. For all the Zn atoms, the typical icosahedral coordination is observed. In the direction of the six- and threefold axes, strong positional disorder is observed as a result of partial substitutions of La atoms by pairs of Mg atoms.

The new ternary phases of La3(Zn0.874Mg0.126)11 and Ce3(Zn0.863Mg0.137)11.

The new ternary intermetallic title compounds, namely trilanthanum undeca(zinc/magnesium), La(3)(Zn(0.874)Mg(0.126))(11), (I), and tricerium undeca(zinc/magnesium), Ce(3)(Zn(0.863)Mg(0.137))(11), (II), are isostructural and crystallize in the orthorhombic La(3)Al(11) structure type. These three phases belong to the same structural family, the representative members of which may be derived from the tetragonal BaAl(4) structure type by a combination of internal deformation and multiple substitution. Compared to the structure of La(3)Al(11), in (I), a significant decrease of 11.9% in the unit-cell b axis and an increase in the other two directions, of 3.6% along a and 5.2% along c, are observed. Such an atypical deformation is caused by the closer packing of atoms in the unit cell due to atom shifts that reflect strengthening of metallic-type bonding. This structural change is also manifested in a significant difference in the coordination around the smaller atoms at the 8l Wyckoff position (site symmetry m). The Al atom in La(3)Al(11) is in a tricapped trigonal prismatic environment (coordination number 9), while the Zn atoms in (I) and (II) are situated in a tetragonal antiprism with two added atoms (coordination number 10).

First approach to nitrogen-containing fused aromatic hydrocarbons as targets for organoelectronics utilizing a new transformation of O-protected diaryl methanols.

A new concise approach for the construction of heteroatom analogues of polycyclic aromatic benzo[g]quinoline, benzo[b]carbazole, and pyrido[b]carbazole systems via diaryl methanols is described. This transformation involves formation of a central benzene ring fused to two aromatic 5- or 6-membered rings of pyrrole and/or pyridine by using a combination of two aromatic aldehydes, of which at least one contains a ring nitrogen. Analysis of the UV and fluorescent properties, Stokes shifts, quantum yields in solution, and pi-stacking interactions in the crystal structures of the new materials was performed. These polycyclic aromatic compounds show potential as small-molecule organoelectronic materials.

2-[(2Z,3E)-2-Hy-droxy-imino-5-phenyl-2,3-dihydro-3-thienyl-idene]-2-phenyl-acetonitrile.

In the crystal structure of the title compound, C(18)H(12)N(2)OS, centrosymmetric dimers are stabilized both by van der Waals inter-actions and by two types of inter-molecular O-H⋯N hydrogen bonds. In addition, an intra-molecular C-H⋯S hydrogen bond is observed. The dihedral angles between the central ring and the two pendant phenyl rings are 7.4 (1) and 45.06 (9)°.

One-pot tandem 1,4-1,2-addition of phosphites to quinolines.

Trialkyl and silylated dialkyl phosphites were evaluated as phosphorus nucleophiles for the addition to quinolines in a strong acidic medium allowing consecutive 1,4- and 1,2-addition breaking up the aromatic stabilisation, thereby leading to 2,4-diphosphono-1,2,3,4-tetrahydroquinolines in one single reaction step in moderate to good yields (2-84%).

4-Methoxy-1-naphthol: chains formed by O-H...O hydrogen bonds and pi-pi stacking interactions.

The structure of 4-methoxy-1-naphthol, C(11)H(10)O(2), (I), contains an intermolecular O-H...O hydrogen bond which links the molecules into a simple C(2) chain running parallel to the shortest crystallographic b axis. This chain is reinforced by intermolecular pi-pi stacking interactions. Comparisons are drawn between the crystal structure of (I) and those of several of its simple analogues, including 1-naphthol and some monosubstituted derivatives, and that of its isomer 7-methoxy-2-naphthol. This comparison shows a close similarity in the packing of the molecules of its simple analogues that form pi-stacks along the shortest crystallographic axes. A substantial spatial overlap is observed between adjacent molecules in such stacks. In this group of monosubstituted naphthols, the overlap depends mainly on the position of the substituents carried by the naphthalene moiety, and the extent of the overlap depends on the substituent type. By contrast with (I), in the crystal structure of the isomeric 7-methoxy-2-naphthol there are no O-H...O hydrogen bonds or pi-pi stacking interactions, and sheets are formed by O-H...pi and C-H...pi interactions.

5-Amino-1-naphthol: two-dimensional sheets built up from R(4)(4)(18) rings formed by O-H...N, N-H...O and pi-pi interactions.

The crystal structure of the title compound, C(10)H(9)NO, (I), contains intermolecular O-H...N and N-H...O hydrogen bonds which together form sheets parallel to the (001) plane containing rings with an unusual R(4)(4)(18) motif. These rings are additionally stabilized by an intermolecular pi-pi stacking interaction. The significance of this study lies in the comparison drawn between the molecular structure of (I) and those of related compounds (1,5-diaminonaphthalene, 8-amino-2-naphthol, 3-amino-2-naphthol and aniline), which shows a close similarity in the noncoplanar orientation of the amine group and the aromatic moiety. Comparison of the crystal structures of (I) and several of its simple analogues (1-naphthol, naphthalene-1,4-diol, naphthalene-1,5-diol and 4-chloro-1-naphthol) shows a close similarity in the packing of the molecules, which form pi-stacks along the shortest crystallographic axes with a substantial spatial overlap between adjacent molecules.

4-Chloro-1-naphthol.

Molecules of the title compound, C(10)H(7)ClO, (I), are connected by a single strong O-H...O hydrogen bond into a simple C(2) chain, which runs parallel to the c axis and is additionally stabilized by intermolecular pi-pi stacking interactions. The significance of this study lies in the comparison drawn between the crystal structure of (I) and those of several of its simple analogues. This comparison shows a close similarity in the packing of the molecules that form pi-stacks along the shortest crystallographic axes. A substantial spatial overlap is observed between adjacent molecules in such a pi-stack, depending mainly on the kind of substituent.

Naphthalene-1,6-diol: a three-dimensional framework built from O-H...O, O-H...pi and C-H...O hydrogen bonds.

The asymmetric unit of the title compound, C(10)H(8)O(2), contains two practically planar symmetry-independent molecules linked by one O-H...O hydrogen bond. Molecules are further linked into a three-dimensional network, which is built from R(6)(6)(36), R(6)(6)(18), R(6)(6)(30) and R(4)(4)(26) rings formed by the combined effect of three O-H...O and one C-H...O hydrogen bond. This network is additionally stabilized by an O-H...pi interaction.