Microarrays are powerful tools in biomedical research and have become indispensable for high-throughput multiplex analysis, especially for DNA and protein analysis. The basis for all microarray processing and fabrication is surface modification of a chip substrate and many different strategies to couple probe molecules to such substrates have been developed. We present here a critical assessment of typical biochip generation processes from a surface science point of view. While great progress has been made from a molecular biology point of view on the development of qualitative assays and impressive results have been obtained on the detection of rather low concentrations of DNA or proteins, quantitative chip-based assays are still comparably rare. We argue that lack of stable and reliable deposition chemistries has led in many cases to suboptimal quantitative reproducibility, impeded further progress in microarray development and prevented a more significant penetration of microarray technology into the diagnostic market. We suggest that surface-attached hydrogel networks might be a promising strategy to achieve highly sensitive and quantitatively reproducible microarrays.

: Tubulin polymerization inhibitors (TPIs) are promising ligands utilized in chemotherapy for modern cancer treatment. However, the current TPIs exhibit many serious side effects that may pose limitations in chemotherapy. Combretastatin A-4 (CA-4) is a natural TPI that binds at the colchicine binding site located on microtubules. The only cis isomer of CA-4 is bio-active; however, due to its short half-life, it isomerizes quickly to its bio-inactive trans geometric isomer. Preventing shortcomings of CA-4, azobenzene based CA-4, called azo-CA-4 (azo-CA-4), identified as a novel TPI. The geometric isomerization of azo-CA-4 can be controlled upon exposure of ultraviolet (UV) light to remotely control its bioactivity. Cis-azo-CA-4 is 200-500 times more active (IC50 = 0.2-10 µM) than trans-azo-CA-4 (IC50 = 50-110 µM) against various cancer cell lines. Photo-pharmacology uses light to control drug activity, introduce a unique mechanism to develop novel photo-responsive TPIs. Further, the green chemistry approach using ethanol and water as a green solvent in the synthesis of azo-CA-4 delivers advanced methodology in novel TPI development .

The Z isomer of azobenzene exhibits nonbonded interactions between ortho substituents on adjacent phenyl groups. For o,o′‐difluoroazobenzene derivatives, through‐space 19F‐19F spin‐spin coupling is observed. The coupling constant decreases as the nuclear magnetic resonance probe temperature is decreased culminating in collapse to a single peak. We have used density functional theory and X‐ray crystallography to argue that phenyl group rotation is responsible for this loss of through‐space coupling. We experimentally measured phenyl rotation barriers in the range of 37 to 44 kJ/mol for o,o′‐difluoroazobenzene derivatives. These rotation barriers are qualitatively similar to literature experimental values for fluxional systems but higher than calculated values for Z‐azobenzene. This is the only project in 35 years that I discussed with J.D.R. This mechanistic interpretation of an unusual nuclear magnetic resonance phenomenon is a classic physical organic investigation inspired by my training with Roberts. I tell this scientific story interwoven with a few observations about working with Roberts.