Structures, Phase Behavior, and Fluorescent Properties of 3-Phenyl-1-(pyridin-2-yl)-1H-pyrazol-5-amine and Its ZnCl2 Complex.

The synthesis of the asymmetric ligand 3-phenyl-1-(pyridin-2-yl)-1H-pyrazol-5-amine (L1) and its single-crystal X-ray structure are reported. L1 displays crystallographic symmetry (orthorhombic, Pccn) higher than its molecular symmetry (point group C1) and also displays supercooling, with a difference in the melting and solidification points of over 100 °C. Upon complexation with ZnCl2, L1 engages in both primary cation and secondary anion coordination via hydrogen bonding, and the complex exhibits a room-to-low-temperature single crystal-to-crystal phase transition. The ZnCl2 complex becomes a birefringent fluid mixed with crystalline domains at high temperatures, as detected by polarized optical microscopy. Examination of the photoluminescence properties showed that the emission intensity increased and a pronounced bathochromic shift was observed in the emission maximum upon going from solution to the solid state, for both the ligand and complex, consistent with aggregation-induced emission behavior.

Influencing the Optoelectronic Properties of a Heteroleptic Iridium Complex by Second-Sphere H-Bonding Interactions.

The use of a new second-sphere coordination methodology for emission color tuning of iridium complexes is presented. We demonstrate that a complementary H-bonding guest molecule binding through contiguous triple H-bonding interactions can induce a shift in the emission of the iridium complex from green to blue without the need to alter the ligand structure around the metal center, while simultaneously increasing the photoluminescence quantum yield in solution. The association constant for this host-guest interaction was determined to be Ka = 4.3 × 103 M-1 in a solution of 2% dimethyl sulfoxide in chloroform by UV-vis titration analysis and the impact of the hydrogen bonding interaction further probed by photoluminescence, electrochemical, and computational methods. Our findings suggest that directed self-assemblies are an effective approach to influencing emission properties of phosphorescent iridium(III) complexes.

Elucidation of Charge Contribution in Iridium-Chelated Hydrogen-Bonding Systems.

We present two iridium complexes 1H + and 2H + that contain cationic ligands to extend the knowledge of charge-assisted hydrogen bonding (CAHB), which counts among the strongest non-covalent bonding interactions. Upon protonation, both complexes were converted into new hydrogen-bonding arrays with various selectivity for respective H-bonding partners. This study compares the association strengths of four hydrogen-bonding co-systems, emphasizing the roles of CAHB in supramolecular systems. We determined that the cationic charge in these systems contributed up to 2.7 kJ mol-1 in the H-bonding complexation processes.

A pH-Switchable Triple Hydrogen-Bonding Motif.

A stimuli responsive linear hydrogen bonding motif, capable of in situ protonation and deprotonation, has been investigated. The interactions of the responsive hydrogen bonding motif with complementary partners were examined through a series of 1H NMR experiments, revealing that the recognition preference of the responsive hydrogen bonding motif in a mixture can be switched between two states.

Thiourea and Guanidine Compounds and Their Iridium Complexes in Drug-Resistant Cancer Cell Lines: Structure-Activity Relationships and Direct Luminescent Imaging.

Thiourea and guanidine units are found in nature, medicine, and materials. Their continued exploration in applications as diverse as cancer therapy, sensors, and electronics means that their toxicity is an important consideration. Iridium complexes present new opportunities for drug development and imaging in terms of structure and photoactivity. We have systematically synthesised a set of thiourea and guanidine compounds and iridium complexes thereof, and elucidated structure-activity relationships for cellular toxicity in three ovarian cancer cell lines and their cisplatin-resistant sub-lines. We have been able to use the intrinsic luminescence of iridium complexes to visualise the effect of both structure alteration and cellular resistance mechanisms. These findings provide starting points for the development of new drugs and consideration of safety issues for novel thiourea-, guanidine-, and iridium-based materials.

ABCB1 as predominant resistance mechanism in cells with acquired SNS-032 resistance.

The CDK inhibitor SNS-032 had previously exerted promising anti-neuroblastoma activity via CDK7 and 9 inhibition. ABCB1 expression was identified as major determinant of SNS-032 resistance. Here, we investigated the role of ABCB1 in acquired SNS-032 resistance. In contrast to ABCB1-expressing UKF-NB-3 sub-lines resistant to other ABCB1 substrates, SNS-032-adapted UKF-NB-3 (UKF-NB-3rSNS- 032300nM) cells remained sensitive to the non-ABCB1 substrate cisplatin and were completely re-sensitized to cytotoxic ABCB1 substrates by ABCB1 inhibition. Moreover, UKF-NB-3rSNS-032300nM cells remained similarly sensitive to CDK7 and 9 inhibition as UKF-NB-3 cells. In contrast, SHEPrSNS-0322000nM, the SNS-032-resistant sub-line of the neuroblastoma cell line SHEP, displayed low level SNS-032 resistance also when ABCB1 was inhibited. This discrepancy may be explained by the higher SNS-032 concentrations that were used to establish SHEPrSNS-0322000nM cells, since SHEP cells intrinsically express ABCB1 and are less sensitive to SNS-032 (IC50 912 nM) than UKF-NB-3 cells (IC50 153 nM). In conclusion, we show that ABCB1 expression represents the primary (sometimes exclusive) resistance mechanism in neuroblastoma cells with acquired resistance to SNS-032. Thus, ABCB1 inhibitors may increase the SNS-032 efficacy in ABCB1-expressing cells and prolong or avoid resistance formation.