Heterocycles as supramolecular handles for crystal engineering: a case study with 7-(diethylamino)coumarin derivatives.

In this study, we present the synthesis and detailed solid-state structural characterization of a Schiff-base-bridged derivative of 7-(diethylamino)coumarin (7-DAC), a molecular block displaying repetitive aggregation modes in the solid state despite being attached to broadly different molecular frameworks. To map the supramolecular habits of this unconventional moiety, we carry out a comparative analysis of the crystal packing in a curated dataset of 50 molecules decorated with the 7-DAC group, retrieved from the literature. We uncover that self-recognition of the 7-DAC moiety has two main components: a set of directional C-H⋯O interactions between neighboring coumarins, and antiparallel dipole-dipole interactions, taking the form of distinct π-stacking modes. The pendant 7-diethylamino group is key to the behavior of 7-DAC, favoring its solubilization through its conformational flexibility in solution, while in the crystalline matrix, it acts as a structural spacer that favors π-stacking interactions. Our findings present a comprehensive analysis of the preferential arrangements of the 7-DAC fragment in various (supra)molecular scenarios, confirming that it is (i) a mobile but mostly planar group, (ii) a group prone to antiparallel aggregation, and (iii) up to 90% likely to pack via π-stacking supported by hydrogen-bonding interactions. These findings enrich the palette of supramolecular motifs available for the bottom-up design of organic materials and their programmed construction.

Enhanced Host-Guest Association and Fluorescence in Copolymers from Copper Salphen Complexes by Supramolecular Internalization of Anions.

Invited for this month's cover are Prof. Escárcega-Bobadilla and Prof. Zelada-Guillén, collaborators from the National Autonomous University of Mexico (UNAM). The cover picture shows the X-ray structure of a chartreuse fluorescent Salphen-Cu complex that upon copolymerization receives dielectric protection from the rest of the chain in solution. This enables cyan luminescence at higher intensity via anion-guest engulfment which renders dimmer-like turn-on emission. More information can be found in the Research Article by G. Zelada-Guillén, M. V. Escárcega-Bobadilla, and co-workers.

Enhanced Host-Guest Association and Fluorescence in Copolymers from Copper Salphen Complexes by Supramolecular Internalization of Anions.

We describe the synthesis, crystallographic characterization of a new Cu-Salphen compound and its use as a host Lewis-acid against guest anions in two versions: a) free molecule, b) copolymerized with methyl methacrylate:n-butyl acrylate (1 : 4-wt.) as protective co-monomers. Higher contents in Cu-Salphen yielded larger and more homogeneous polymer sizes. Polymer size together with glass transitions, heat capacity, thermal degradation, guest-saturation degrees and host-guest species distribution profiles from spectrophotometric titrations explained growths of up to 630-fold in K11 and 180000-fold in K12 for the host's binding site attributable to a solvophobic protection from the macromolecular structure. Spectrofluorimetry revealed blue-shifted×13-16 larger luminescence for Cu-Salphen in the polymers (λem =488-498 nm) than that of the non-polymerized counterpart (λem =510-543 nm) and "turn-on" blue-shifted enhanced fluorescence upon guest association. We propose a cooperative incorporation of the guests occurring from the outer medium toward internally protected binding site pockets in the random coil polymer conformations.

Turing patterns by supramolecular self-assembly of a single salphen building block.

In the 1950s, Alan Turing showed that concerted reactions and diffusion of activating and inhibiting chemical species can autonomously generate patterns without previous positional information, thus providing a chemical basis for morphogenesis in Nature. However, access to these patterns from only one molecular component that contained all the necessary information to execute agonistic and antagonistic signaling is so far an elusive goal, since two or more participants with different diffusivities are a must. Here, we report on a single-molecule system that generates Turing patterns arrested in the solid state, where supramolecular interactions are used instead of chemical reactions, whereas diffusional differences arise from heterogeneously populated self-assembled products. We employ a family of hydroxylated organic salphen building blocks based on a bis-Schiff-base scaffold with portions responsible for either activation or inhibition of assemblies at different hierarchies through purely supramolecular reactions, only depending upon the solvent dielectric constant and evaporation as fuel.

Reductive desymmetrization of steroid dimers.

NaBH3CN reduction of symmetric dimers in which two steroid units are linked by a 1,4-dimethylidenebenzene moiety followed two different courses: (a) hydrogenation of the benzylic double bond and (b) reductive F ring opening of the side chain. While courses a and b led to symmetrical dimers, the combination of both pathways produced an unsymmetrical dimer that bears different side chains in each half. The exhaustive NMR characterization of all obtained compounds is presented.

Acrylic Polymers Containing a Nickel Salphen Complex: An Approach to Supramolecular and Macromolecular Systems.

Invited for this month's cover are Prof. Martha Escárcega-Bobadilla and Prof. Gustavo Zelada-Guillén, collaborators from the National Autonomous University of Mexico (UNAM). The cover picture shows the structure of a polymerizable Ni-Salphen complex, determined by X-ray crystallography, where the Ni center displays 1:1 and 1:2 host-guest stoichiometries toward anions, both coexisting in solution. Read the full text of the article at 10.1002/cplu.202000471.

Acrylic Polymers Containing a Nickel Salphen Complex: An Approach to Supramolecular and Macromolecular Systems.

The synthesis, characterization and crystallographic analysis is reported of a new Nickel Salphen complex and its radical copolymerization with n-butyl acrylate and methyl methacrylate to produce novel host macromolecules with tunable association against guest anions. Spectrophotometric titrations of the complex and of the polymers revealed that a supramolecular regulation of guest-binding accessibility was enabled by the number of Ni-Salphen units per chain. The latter content in turn, determined the chain size and molecular weight uniformity upon polymerization, and likely increased the strength in interchain/intrachain non-covalent interactions over the nickel center and the acrylic domains. The study also showed that incorporation of the monomer into the acrylic polymer backbone opened the possibility for the nickel binding site to gain access to host:guest stoichiometric discrimination, switching from 1 : 1 (major) and 1 : 2 (minor) both coexisting for the host when in the free form, to mostly 1 : 2 when in the polymerized version.

Two-Photon-Triggered NO Release via a Ruthenium-Nitrosyl Complex with a Star-Shaped Architecture.

We report herein a molecular engineering strategy based on the design of a multipolar ruthenium-nitrosyl (Ru-NO) complex with a three-branched architecture. The three Ru-NO units are introduced at the periphery of a highly π-delocalized truxene core bearing three terpyridine ligands. The two-photon absorption capabilities of the complex were investigated by the Z-scan technique. The strong electronic coupling among the individual arms gives rise to a very strong two-photon absorption response (δ800 nm ∼ 1600 GM), which corresponds to a 16-fold enhancement of the capability of a single-arm reference, thereby promoting an efficient light-driven NO release process in aqueous media.

Synthesis, complete NMR assignment and structural study of a steroidal dimer of 17α-ethynyl-5α,10α-estran-17ß-ol with diethynylbenzene spacer.

A phenylene-bridged steroidal dimer derived from 17α-ethynyl-5α,10α-estran-17ß-ol with molecular rotor-like architecture was synthesized to investigate the supramolecular interactions directing the crystallization of these systems. Structures with varying importance in complementarity between H-bonding and hydrophobic interactions can be observed directing the packing of the obtained crystals, depending on the synthetic stage, though conserving the same space group for both systems. Such behavior clearly shows the versatility achievable using steroids as crystal packing directors. Alongside this structural study, the complete NMR assignment is presented for the dimer, and precursors, in which the steroids present an unconventional and noteworthy A-B ring fusion.

Synthesis of a Novel Zn-Salphen Building Block and Its Acrylic Terpolymer Counterparts as Tunable Supramolecular Recognition Systems.

In this work, we present the synthesis of a novel Zn-Salphen complex containing an allyl group, which was used as building block in the further preparation of a new family of functional terpolymers. These polymers were obtained through radical co-polymerization with methyl metacrylate (MMA) and n-butyl acrylate (nBuA) in different ratios. The supramolecular recognition behavior of each polymer was evaluated via potentiometric measurements against selected anions in aqueous media. Interestingly, this proof of concept study shows that these systems were selective against only fluoride (F-) or both, fluoride and acetate (OAc-), by tailoring the relative content of Zn-Salphen monomer, thus making them a promising starting point for modular design of chemical sensors through straightforward synthetic approaches.

Experimental-Theoretical Approach to the Adsorption Mechanisms for Anionic, Cationic, and Zwitterionic Surfactants at the Calcite-Water Interface.

The adsorption of surfactants (DTAB, SDS, and CAPB) at the calcite-water interface was studied through surface zeta potential measurements and multiscale molecular dynamics. The ground-state polarization of surfactants proved to be a key factor for the observed behavior; correlation was found between adsorption and the hard or soft charge distribution of the amphiphile. SDS exhibits a steep aggregation profile, reaching saturation and showing classic ionic-surfactant behavior. In contrast, DTAB and CAPB featured diversified adsorption profiles, suggesting interplay between supramolecular aggregation and desorption from the solid surface and alleviating charge buildup at the carbonate surface when bulk concentration approaches CMC. This manifests as an adsorption profile with a fast initial step, followed by a metastable plateau and finalizing with a sharp decrease and stabilization of surface charge. Suggesting this competition of equilibria, elicited at the CaCO3 surface, this study provides atomistic insight into the adsorption mechanism for ionic surfactants on calcite, which is in accordance with experimental evidence and which is a relevant criterion for developing enhanced oil recovery processes.

Design, synthesis, in vitro evaluation and preliminary SAR studies of N-(2-(heteroaryloxy)propyl)phenothiazines against Rhipicephalus microplus cattle tick.

A family of 15 N-substituted phenothiazines was designed, synthesized and their acaricidal activity against Rhipicephalus microplus was determined in vitro. The synthetic methodology is simple and can be employed in multigram scale. The rationale for the structure-based design of these compounds is the potential for azines and phenothiazine to engage in π-π interactions; these fragments, joined together by a short, flexible alkoxide linker, structurally resemble phenothiazine-based cholinesterase inhibitors, while their weak basicity implies a neutral active form, rather than a cationic one, thus facilitating penetration of the cuticle of ticks. One compound displayed excellent acaricidal activity (LD50=0.58 µg/mL). Preliminary SAR analysis suggests that the activity is influenced by the presence of a weakly basic nitrogen atom, as well as the substitution pattern within the heterocycles.

Synthesis of 24-phenyl-24-oxo steroids derived from bile acids by palladium-catalyzed cross coupling with phenylboronic acid. NMR characterization and X-ray structures.

Palladium-catalyzed cross coupling of phenyboronic acid with acetylated bile acids in which the carboxyl functions have been activated by formation of a mixed anhydride with pivalic anhydride afforded moderate to good yield of 24-phenyl-24-oxo-steroids. Unambiguous assignments of the NMR signals were made with the aid of combined 1D and 2D NMR techniques. X-ray diffraction studies confirmed the obtained structures.

Downregulation of SnoN oncoprotein induced by antibiotics anisomycin and puromycin positively regulates transforming growth factor-ß signals.

BACKGROUND: SnoN and Ski proteins function as Smad transcriptional corepressors and are implicated in the regulation of diverse cellular processes such as proliferation, differentiation and transformation. Transforming growth factor-ß (TGF-ß) signaling causes SnoN and Ski protein degradation via proteasome with the participation of phosphorylated R-Smad proteins. Intriguingly, the antibiotics anisomycin (ANS) and puromycin (PURO) are also able to downregulate Ski and SnoN proteins via proteasome. METHODS: We explored the effects of ANS and PURO on SnoN protein downregulation when the activity of TGF-ß signaling was inhibited by using different pharmacological and non-pharmacological approaches, either by using specific TßRI inhibitors, overexpressing the inhibitory Smad7 protein, or knocking-down TßRI receptor or Smad2 by specific shRNAs. The outcome of SnoN and Ski downregulation induced by ANS or PURO on TGF-ß signaling was also studied. RESULTS: SnoN protein downregulation induced by ANS and PURO did not involve the induction of R-Smad phosphorylation but it was abrogated after TGF-ß signaling inhibition; this effect occurred in a cell type-specific manner and independently of protein synthesis inhibition or any other ribotoxic effect. Intriguingly, antibiotics seem to require components of the TGF-ß/Smad pathway to downregulate SnoN. In addition, SnoN protein downregulation induced by antibiotics favored gene transcription induced by TGF-ß signaling. CONCLUSIONS: ANS and PURO require TGF-ß/Smad pathway to induce SnoN and Ski protein downregulation independently of inducing R-Smad2 phosphorylation, which facilitates TGF-ß signaling. GENERAL SIGNIFICANCE: Antibiotic analogs lacking ribotoxic effects are useful as pharmacological tools to study TGF-ß signaling by controlling Ski and SnoN protein levels.

Diacetoxyiodobenzene-mediated synthesis of unnatural furospirostane sapogenins derived from diosgenin and tigogenin.

Two unnatural steroid sapogenins bearing a furospirostane side chain were prepared starting from the readily available spirostane sapogenins, tigogenin and diosgenin following a synthetic protocol that included: (i) introduction of a carbonyl group at position C-23, (ii) diacetoxyiodobenzene-induced F-ring contraction and (iii) LiAlH4 reduction of the newly emerged methoxycarbonyl moiety. The structures of the new compounds were corroborated by NMR and X-ray studies.

Hypervalent-iodine induced quasi-Favorskii C-ring contraction of 12-oxosteroids: a shortcut to C-norsteroids.

Treatment of 12-oxosteroids with PhI(OAc)(2) and KOH in refluxing methanol triggers a quasi-Favorskii C-ring contraction leading to the corresponding 11α-alcoxycarbonyl-C-norsteroids in moderate yields. This constitutes the first one-step synthetic alternative to C-norsteroids starting from 12-oxosteroids.

BF3·Et2O-induced stereoselective aldol reaction with benzaldehyde, and steroid sapogenins and its application to a convenient synthesis of dinorcholanic lactones.

Treatment of steroid sapogenins with benzaldehyde and BF(3)·Et(2)O cleanly produces E-23(23')-benzylidenspirostanes in good yields in a reaction pathway which consists on an aldol reaction followed by a dehydration step. The obtained E-23(23')-benzylidenspirostanes can be easily converted to dinorcholanic lactones by treatment with CrO(3) in acetic acid. The synthetic sequence to dinorcholanic lactones is compatible with the presence of double bonds and carbonyl groups in the steroid framework.

Revisiting 23-iodospirostanes. New facts and full characterization.

In addition to a previous report, the reaction of tigogenin acetate with ICl in refluxing CHCl(3) produced the hitherto unknown 23R-iodotigogenin acetate, bearing an axial iodine atom at C-23 and its already reported 23S-epimer. The same treatment of sarsasapogenin acetate led to a single diasteromer characterized as 23S-iodosarsasapogenin acetate. A full characterization of the obtained compound including (1)H, (13)C NMR, MS and X-ray diffraction is provided.

Synthesis and biological activity of furostanic analogues of brassinosteroids bearing the 5alpha-hydroxy-6-oxo moiety.

Two furostanic analogues of brassinosteroids bearing the 5alpha-hydroxy-6-oxo moiety were synthesized and their biological activity studied using the bean second internode elongation test. One of the compounds produced significant stimulation at doses of 2.5 and 5ng/plant.