Functionalized C3-Symmetric Building Blocks-The Chemistry of Triaminotrimesic Acid.

A series of C3-symmetric fully substituted benzenes were prepared based on alkyl triamino-benzene-tricarboxylates. Starting with a one step-synthesis, the alkyl triamino-benzene-tricarboxylates were synthesized using the corresponding cyanoacetates. The reactivity of these electronically sophisticated compounds was investigated by the formation of azides, the click reaction of the azides and a Sandmeyer-like reaction. Caused by the low stability of triaminobenzenes, direct N-alkylation was rarely reported. The use of the stable alkyl triamino-benzene-tricarboxylates allowed us total N-alkylation under standard alkylation conditions. The molecular structures of the C3-symmetric structures have been corroborated by an X-ray analysis.

Breaking Symmetry Relaxes Structural and Magnetic Restraints, Suppressing QTM in Enantiopure Butterfly Fe2 Dy2 SMMs*.

The {Fe2 Dy2 } butterfly systems can show single molecule magnet (SMM) behaviour, the nature of which depends on details of the electronic structure, as previously demonstrated for the [Fe2 Dy2 (µ3 -OH)2 (Me-teaH)2 (O2 CPh)6 ] compound, where the [N,N-bis-(2-hydroxyethyl)-amino]-2-propanol (Me-teaH3 ) ligand is usually used in its racemic form. Here, we describe the consequences for the SMM properties by using enantiopure versions of this ligand and present the first homochiral 3d/4 f SMM, which could only be obtained for the S enantiomer of the ligand for [Fe2 Dy2 (µ3 -OH)2 (Me-teaH)2 (O2 CPh)6 ] since the R enantiomer underwent significant racemisation. To investigate this further, we prepared the [Fe2 Dy2 (µ3 -OH)2 (Me-teaH)2 (O2 CPh)4 (NO3 )2 ] version, which could be obtained as the RS-, R- and S-compounds. Remarkably, the enantiopure versions show enhanced slow relaxation of magnetisation. The use of the enantiomerically pure ligand suppresses QTM, leading to the conclusion that use of enantiopure ligands is a "gamechanger" by breaking the cluster symmetry and altering the intimate details of the coordination cluster's molecular structure.

Neurological phenotypes in patients with NLRP3-, MEFV-, and TNFRSF1A low-penetrance variants.

BACKGROUND: Neurological manifestations and the co-occurrence of multiple sclerosis (MS) have been reported in patients with autoinflammatory diseases (AID) and variants of the NLRP3-, MEFV-, or TNFRSF1A gene. However, type and frequency of neurological involvement are widely undetermined. METHODS: We assessed clinical characteristics of 151 (108 with MS) patients carrying NLRP3-, MEFV- and TNFRSF1A low-penetrance variants  from the Institute of Clinical Neuroimmunology. We evaluated demographic, genetic, and clinical features with a focus on central nervous system (CNS) involvement including magnetic resonance imaging (MRI) results and cerebrospinal fluid (CSF) data. The disease course of AID patients with MS was compared to a matched MS control group without mutations. RESULTS: The genetic distribution comprised 36 patients (23%) with NLRP3- and 66 patients (43%) with TNFRSF1A low-penetrance variants as well as 53 (34%) patients carrying pathogenic mutations or low-penetrance variants in the MEFV gene. MS patients displayed most frequently the R92Q TNFRSF1A variant (n = 51; 46%) followed by the Q703K NLRP3 variant (n = 15; 14%) and the E148Q substitution (n = 9; 8%) in the MEFV gene. The disease course of MS was not influenced by the genetic variants and did not differ from MS patients (n = 51) without mutations. AID patients without MS most frequently harbored MEFV mutations (n = 19, 43%) followed by NLRP3- (n = 17, 39%) and TNFRSF1A (n = 8, 18%) low-penetrance variants. Sixteen (36%) of them suffered from severe CNS involvement predominantly recurrent aseptic meningoencephalitis and optic neuritis accompanied by abnormal MRI and CSF results. Severe CNS inflammation was associated with the Q703K allele. Headache was a highly prevalent neurological symptom (up to 74%), irrespective of the underlying genetic variation. The NLRP3 cohort without MS more frequently exhibited affections of the cranial nerves (CN) (p = 0.0228) and motor symptoms (p = 0.0455). Elevated acute-phase reactants were detected in all patients, and fever episodes were present in up to 50%. Arthralgias were the most frequently identified constitutional symptom among all subgroups. CONCLUSIONS: Our data highlight the high prevalence of neurological manifestations, including concomitant MS, among NLRP3-, MEFV-, and TNFRSF1A low-penetrance variants. In particular, patients carrying the Q703K NLRP3 variant are at risk for severe CNS inflammation and CN affection.

Photoconductivity in Metal-Organic Framework (MOF) Thin Films.

Photoconductivity is a characteristic property of semi-conductors. Herein, we present a photo-conducting crystalline metal-organic framework (MOF) thin film with an on-off photocurrent ratio of two orders of magnitude. These oriented, surface-mounted MOF thin films (SURMOFs), contain porphyrin in the framework backbone and C60 guests, loaded in the pores using a layer-by-layer process. By comparison with results obtained for reference MOF structures and based on DFT calculations, we conclude that donor-acceptor interactions between the porphyrin of the host MOF and the C60 guests give rise to a rapid charge separation. Subsequently, holes and electrons are transported through separate channels formed by porphyrin and by C60 , respectively. The ability to tune the properties and energy levels of the porphyrin and fullerene, along with the controlled organization of donor-acceptor pairs in this regular framework offers potential to increase the photoconduction on-off ratio.

Two-photon absorption in a series of 2,6-disubstituted BODIPY dyes.

We report on the two-photon absorption spectra of a series of 2,6-disubstituted BODIPY dyes. Depending on the substituents, we observe increasing two-photon absorption cross sections with values up to 350 GM compared to 70 GM in the unsubstituted dye. Quantum chemical calculations are performed to assign the absorption bands and to understand the factors controlling the size of the two-photon absorption cross section. Both the maximum of the two-photon absorption band as well as the red-shift of the whole spectrum correlate with the ability of the substituents to extend the π-electron system of the dye. The above-mentioned intense two-photon absorption band corresponds to the absorption of photons with 1.3 eV, which is at the first near-infrared transparency window for biological tissues. The dyes could thus be suitable for bio-imaging applications.

Ruthenium-catalyzed C-H activation of thioxanthones.

Thioxanthones - being readily available in one step from thiosalicylic acid and arenes - were used in ruthenium-catalyzed C-H-activation reaction to produce 1-mono- or 1,8-disubstituted thioxanthones in good to excellent yields. Scope and limitation of this reaction are presented.

Antibacterial activity of sulfamethoxazole transformation products (TPs): general relevance for sulfonamide TPs modified at the para position.

Sulfonamide antibiotics undergo transformation in the aquatic environment through biodegradation, photolysis, or hydrolysis. In this study, the residual antibacterial activity of 11 transformation products (TPs) of sulfamethoxazole (SMX) was investigated with regard to their in vitro growth and luminescence inhibition on Vibrio fischeri (30 min and 24 h exposure). Two transformation products, 4-hydroxy-SMX and N(4)-hydroxy-acetyl-SMX, were synthesized in-house and confirmed by nuclear magnetic resonance and high-resolution mass spectrometry. Results of individual compound experiments showed that TPs modified at the para amino group still exhibit clear antibacterial effects, whereas TPs resulting from breakdown of the SMX structure lost this mechanism of action. 4-NO2- and 4-OH-SMX were found to inhibit growth to a clearly greater extent than the parent compound, SMX. In contrast, the N(4)-acetyl- and N(4)-hydroxy-acetyl-derivatives retain less than 10 and 5% of the effect of SMX on growth and luminescence inhibition, respectively. The effect of a mixture of para-modified TPs was observed to be additive. Considering the homologous series of sulfa drugs widely prescribed and their common mechanism of action, the potential environmental impact must consider the total amount of sulfonamide antibiotics and their derivative TPs, which might end up in a water body. Extrapolating the results obtained here for the para TPs of SMX to other sulfa drugs and determining the persistence and occurrence of these compounds in the aquatic environment is required for improved risk assessment.

Azaporphine guest-host complexes in solution and gas-phase: evidence for partially filled nanoprisms and exchange reactions.

Supramolecular guest-host complexes comprising various azaporphines stacked in a coordination nanoprism consisting of tris(4-pyridyl)triazines as panels, 1,4-bis(pyridyl)benzenes as pillars and (en)Pd as hinges were synthesized according to the procedure of Fujita and coworkers and characterized as ions in the gas-phase by high-resolution electrospray ionization mass spectrometry and collision induced dissociation as well as in solution by analytical ultracentrifugation. Apart from fully filled nanoprisms we have also prepared and observed partially filled as well as empty congeners in aqueous solutions. Upon mixing room temperature solutions of two types of nanoprisms, we observe that azaporphine guest exchange reactions occur on a timescale of minutes, indicating that the formation of the guest-host complexes is reversible.

Collision Induced Dissociation of Benzylpyridinium-Substituted Porphyrins: Towards a Thermometer Scale for Multiply Charged Ions?

We have determined breakdown curves for a range of multiply charged benzylpyridinium-substituted porphyrin cations by collision induced dissociation measurements (CID) as mediated by resonant pulsed radio-frequency (rf) excitation in a helium-filled linear ion trap. Measurements were compared with the predictions of DFT calculations. We find a linear correlation between experimental fragmentation thresholds (in instrumental units of "normalized collision energy") and theoretical dissociation energies, suggesting that these species can be used as calibrants to gauge the fragmentation energetics of closely related systems. We have confirmed this by also studying the fragmentation thresholds of metalloporphyrin-based ions - including multiply negatively charged metalloporphyrin oligomers. Unfortunately, the slope of the linear correlation obtained for benzylpyridinium-substituted porphyrin multications differs significantly from that obtained by us for a set of smaller, singly charged substituted benzylpyridines put forward as "thermometer" ions in previous work. Multiplying the threshold energies in an ad hoc fashion by the ion charge basically reconciles both calibration curves. We conclude that one should use caution when applying small, singly charged benzylpyridines as calibrants to gauge the CID of large, multiply charged ions in ion-trap mass spectrometers. Graphical Abstract.

High Antimicrobial Activity of Metal-Organic Framework-Templated Porphyrin Polymer Thin Films.

Development of surface coatings with high antimicrobial activity is urgently required to fight bacteria and other microorganisms on technical and hygiene relevant surfaces. Control over structure and topology of the surface coatings, combined with the ability to include functional molecules within the structure, is crucial for optimizing their performance. Herein, we describe a novel strategy to synthesize structurally well-defined porphyrin polymer thin films via a template approach. In this approach, bisazido-functionalized porphyrin molecules are preorganized within a metal-organic framework (MOF) structure. Afterward, porphyrin units within the MOF are covalently connected via a secondary linker. Removal of the metal ions of the MOF results in water-stable porphyrin polymer thin films that demonstrate high antibacterial activity against pathogens via visible-light-promoted generation of reactive oxygen species. In addition, this approach offers the inherent possibility to incorporate guest molecules within the structures, to functionalize the surface with biomolecules, and to create hierarchically structured materials.

Tunable molecular separation by nanoporous membranes.

Metal-organic frameworks offer tremendous potential for efficient separation of molecular mixtures. Different pore sizes and suitable functionalizations of the framework allow for an adjustment of the static selectivity. Here we report membranes which offer dynamic control of the selectivity by remote signals, thus enabling a continuous adjustment of the permeate flux. This is realized by assembling linkers containing photoresponsive azobenzene-side-groups into monolithic, crystalline membranes of metal-organic frameworks. The azobenzene moieties can be switched from the trans to the cis configuration and vice versa by irradiation with ultraviolet or visible light, resulting in a substantial modification of the membrane permeability and separation factor. The precise control of the cis:trans azobenzene ratio, for example, by controlled irradiation times or by simultaneous irradiation with ultraviolet and visible light, enables the continuous tuning of the separation. For hydrogen:carbon-dioxide, the separation factor of this smart membrane can be steplessly adjusted between 3 and 8.