Pseudomonas aeruginosa is a Gram-negative bacterium, which causes opportunistic infections in immuno-compromised individuals. Due to its multiple resistances toward antibiotics, the development of new drugs is required. Interfering with Quorum Sensing (QS), a cell-to-cell communication system, has shown to be highly efficient in reducing P. aeruginosa pathogenicity. One of its QS systems employs Pseudomonas Quinolone Signal (PQS) and 4-hydroxy-2-heptylquinoline (HHQ) as signal molecules. Both activate the transcriptional regulator MvfR (Multiple Virulence Factor Regulator), also called PqsR, driving the production of QS molecules as well as toxins and biofilm formation. The aim of this work was to elucidate the effects of QS inhibitors (QSIs), such as MvfR antagonists and PqsBC inhibitors, on the biosynthesis of the MvfR-regulated small molecules 2′-aminoacetophenone (2-AA), dihydroxyquinoline (DHQ), HHQ, PQS, and 4-hydroxy-2-heptylquinoline-N-oxide (HQNO). The employed synthetic MvfR antagonist fully inhibited pqs small molecule formation showing expected sigmoidal dose-response curves for 2-AA, HQNO, HHQ and PQS. Surprisingly, DHQ levels were enhanced at lower antagonist concentrations followed by a full suppression at higher QSI amounts. This particular bi-phasic profile hinted at the accumulation of a biosynthetic intermediate resulting in the observed overproduction of the shunt product DHQ. Additionally, investigations on PqsBC inhibitors showed a reduction of MvfR natural ligands, while increased 2-AA, DHQ and HQNO levels compared to the untreated cells were detected. Moreover, PqsBC inhibitors did not show any significant effect in PA14 pqsC mutant demonstrating their target selectivity. As 2-AA is important for antibacterial tolerance, the QSIs were evaluated in their capability to attenuate persistence. Indeed, persister cells were reduced along with 2-AA inhibition resulting from MvfR antagonism, but not from PqsBC inhibition. In conclusion, antagonizing MvfR using a dosage capable of fully suppressing this QS system will lead to a favorable therapeutic outcome as DHQ overproduction is avoided and bacterial persistence is reduced.

The structural dynamics of two pairs of [2]rotaxanes were compared using variable-temperature NMR. Each rotaxane had a surrounding tetralactam macrocycle with either 2,6-pyridine dicarboxamide or isophthalamide bridging units. Differences were observed in two types of rotational processes: spinning of the phenylene wall units in the surrounding macrocycle of squaraine rotaxanes and macrocycle pirouetting in xanthone rotaxanes. The rotaxanes with macrocycles containing 2,6-pyridine dicarboxamide bridges exhibited higher rotational barriers due to a cavity contraction effect, which disfavored macrocycle breathing.

The development of novel antimycobacterial agents against Mycobacterium tuberculosis (Mtb) is urgently required due to the appearance of multidrug resistance (MDR) combined with complicated long‐term treatment. CYP121 was shown to be a promising novel target for inhibition of mycobacterial growth. In this study, we describe the rational discovery of new CYP121 inhibitors by a systematic screening based on biophysical and microbiological methods. The best hits originating from only one structural class gave initial information about molecular motifs required for binding and activity. The initial screening procedure was followed by mode‐of‐action studies and further biological characterizations. The results demonstrate superior antimycobacterial efficacy and a decreased toxicity profile of our frontrunner compound relative to the reference compound econazole. Due to its low molecular weight, promising biological profile, and physicochemical properties, this compound is an excellent starting point for further rational optimization.

An important paradigm in anti-infective research is the antivirulence concept. Pathoblockers are compounds which disarm bacteria of their arsenal of virulence factors. PqsR is a transcriptional regulator controlling the production of such factors in Pseudomonas aeruginosa, most prominently pyocyanin. In this work, a series of tool compounds based on the structure of the natural ligand 2-heptyl-4-quinolone (HHQ) were used for probing the structure-functionality relationship. Four different profiles are identified namely agonists, antagonists, inverse agonists and biphasic modulators. Molecular docking studies revealed that each class of the PqsR modulators showed distinctive interactions in the PqsR binding domain. It was found that the substituents in position 3 of the quinolone core act as a switch between the different profiles, according to their ability to donate or accept a hydrogen bond, or form a hydrophobic interaction. Finally, it was shown that only inverse agonists were able to strongly inhibit pyocyanin production.

We synthesised a new N-benzylaza-21-crown-7 ether 5 with a dihydroxy coumarin as a fluorescence sensor and investigated the binding behaviour towards alkali metal cations in methanol by fluorescence titrations. The association constants are within one order of magnitude, with the exception of sodium. Potassium is the preferred binding partner (K(Na)=330 M(-1); K(K)=8600 M(-1); K(Rb)=8200 M(-1); K(Cs)=4400 M(-1)). The corresponding aza-21-crown-7 ether (6) was attached by a methylene unit to a resorcarene to give fluorescent calix crown ether 12. The binding abilities of the calix crown ether towards alkali metal ions in methanol have also been investigated, and an increasing complex stability, distinct for potassium and rubidium in comparison with 5, was found: K(Na)=440 M(-1); K(K)=110,000 M(-1); K(Rb)=63,000 M(-1); K(Cs)=20,000 M(-1). Like bis(crown ether)s, a cooperative complexation of the crown ether and the cavitand scaffold can be assumed. The proposed complex geometry is supported by Kohn-Sham DFT calculations for the potassium and caesium complexes.

N-Ethylmaleimide and maleic anhydride add to the interior face of one anthracene wall with unusual 1,4-regioselectivity, whereas singlet oxygen adds to both anthracene walls with 9,10-regioselectivity.

Calculations based on (occupation constrained) density functional theory using local as well as hybrid functionals to describe the electron-electron exchange and correlation are combined with many-body perturbation theory in order to determine and rationalize the electronic and optical excitation properties of 2-aminopyrimidinesilver(I) based organic semiconductors and their parent molecules. Large quasiparticle shifts and exciton binding energies of about 4 eV are found in the aminopyrimidine molecules. Both the quasiparticle blueshift and the excitonic redshift are reduced upon crystal formation. They cancel each other partially and thus allow for a meaningful description of the molecular and crystal optical response within the independent-particle approximation. We find a surprisingly strong influence of local-field effects as well as resonant-nonresonant coupling terms in the electron-hole Hamiltonian on the optical properties. The calculations reproduce well measured data and allow for identifying chemical trends with respect to the organic building blocks of the crystals.

We present first principle studies on the rational design of an acridine/N‐methylacridinium dye (Acr/MeAcr+) substituted terpyridine ligand to investigate if these chromophores can act as triplet‐energy storage units in bis(terpyridine) ruthenium(II) complexes. We studied the influence of the dye form (Acr/MeAcr+) as well as the interconnecting linker unit (none, 4‐phenyl, or 5‐thien‐2‐yl) and investigated these aspects by steady‐state/time‐resolved spectroscopy, cyclic voltammetry, X‐ray structure analysis, and DFT calculations.