The Lin Group works on a variety of interdisciplinary research projects that are relevant to important societal issues like the environment and sustainability, alternative energy sources, and human health. We design metal-organic frameworks from metal ions with well-defined geometry and organic bridging ligands. These porous hybrid materials can be used for gas storage and enantioselective heterogeneous catalysis.
We also develop new hybrid nanomaterials for biological and biomedical applications. These include contrast agents for magnetic resonance, optical, and computed tomography imaging, for early diagnosis of disease, as well as targeted delivery of drugs for cancer therapy. Nanoparticles are tunable and can be surface-modified for controlled release or functionalized with affinity molecules for target-specific delivery of a high payload of a diagnostic or therapeutic agent.
The Meyer Lab has a wide range of research interests based in transition metal chemistry. We have multiple ongoing collaborations with professors in both biological to physical chemistry. Members of the Meyer lab are closely involved with other groups in the Chemistry department, including Lin, Papanikolas, Templeton, Thorp, and You.
The unifying theme of our many projects is energy conversion. By studying the basic principles of electron transfer, excited states, and redox catalysis, we hope to advance the frontier of knowledge in renewable energy research. For example, we are currently investigating mechanisms of proton-coupled electron transfer, in order to understand how water is oxidized by Photosystem II during photosynthesis.
The chromatin folding problem is an exciting and rich field for modern research. On the most basic level, chromatin fiber consists of a collection of protein-nucleic acid complexes, known as nucleosomes, joined together by segments of linker DNA. Understanding how the cell successfully compacts meters of highly charged DNA into a micrometer size nucleus while still enabling rapid access to the genetic code for transcriptional processes is a challenging goal.
In an article published in JACS, the Papoian Group, discusses the way mobile ions condense around the nucleosome core particle, as revealed by an extensive all-atom molecular dynamics simulation. Overall, this research facilitates a better understanding of the way ionic and hydration interactions within a nucleosome may affect internucleosomal interactions in higher order chromatin fibers.
Protein−protein interaction is the fundamental step of biological signal transduction. Interacting proteins find each other by diffusion. To gain insight into diffusion under the crowded conditions found in cells, researchers in the Pielak Group used nuclear magnetic resonance spectroscopy (NMR) to measure the effects of solvent additives on the translational and rotational diffusion of the 7.4 kDa globular protein, chymotrypsin inhibitor 2.
The additives were glycerol and the macromolecular crowding agent, polyvinyl pyrrolidone (PVP). As published in the Journal of Physical Chemistry B, both translational diffusion and rotational diffusion decrease with increasing solution viscosity. For glycerol, the decrease obeys the Stokes−Einstein and Stokes−Einstein Debye laws. Three types of deviation are observed for PVP: the decrease in diffusion with increased viscosity is less than predicted, this negative deviation is greater for rotational diffusion, and the negative deviation increases with increasing PVP molecular weight.
Researchers in the Waters Group, as published in JACS, demonstrate how phosphorylated amino acids were incorporated into a designed β-hairpin peptide to study the effect on β-hairpin structure when the phosphate group is positioned to interact with a tryptophan residue on the neighboring strand. The three commonly phosphorylated residues in biological systems, serine, threonine, and tyrosine, were studied in the same β-hairpin system.
It was found that phosporylation destabilizes the hairpin structure by approximately 1.0 kcal/mol, regardless of the type of phosphorylated residue. In contrast, destabilization due to glutamic acid was about 0.3 kcal/mol. Double mutant cycles and pH studies are consistent with a repulsive interaction as the source of destabilization. These findings demonstrate a novel mechanism by which phosphorylation may influence protein structure and function.
Serotonin, also known as 5-HT is an important molecule in the brain that is implicated in mood and emotional processes. Although there is a heavy pharmaceutical emphasis on serotonin's involvement in many neurological disorders, in vivo, its dynamic release and uptake kinetics are poorly understood. This is due to a lack of analytical techniques for its rapid measurement. Whereas fast-scan cyclic voltammetry with carbon fiber microelectrodes is used frequently to monitor subsecond dopamine release in freely moving and anesthetized rats, the electrooxidation of serotonin forms products that quickly polymerize and irreversibly coat the carbon electrode surface.
In a paper published in Analytical Chemistry, the Wightman Group identifies the root of this fouling to not only be due to serotonin, but also to the negatively charged extracellular metabolites of serotonin, present in 200−1000 times the concentration of serotonin in vivo. To impede access of these negatively charged species, a thin layer of Nafion, a cation exchange polymer, was electrodeposited onto cylindrical carbon-fiber microelectrodes. The team visually confirmed the presence of the Nafion film using scanning electron microscopy and showed that the signals for negatively charged species were diminished. Interestingly, the properties of the Nafion also increased sensitivity to serotonin, providing an electrochemical signature of serotonin that could be verified in vitro. In vivo, the team used physiological, anatomical, and pharmacological evidence to validate the signal as serotonin. Using Nafion-modified microelectrodes, the Wightman Group presents the first endogenous recording of serotonin in the mammalian brain.
The platinum-containing chemotherapeutic cisplatin is the first-line treatment for many types of cancer, but results in a myriad of disparaging dose-limiting side effects, such as nephrotoxicity and neurotoxicity. Nanomaterials have shown great promise in selectively delivering chemotherapeutics to tumors to reduce these side effects and to increase therapeutic indices. As reported in JACS, the Lin Group has developed a novel nanovector platform based on nanoscale metal-organic frameworks, NMOFs, for delivering chemotherapeutics and imaging contrast agents.
NMOFs are materials crafted from metals and organic bridging ligands, and can be engineered to contain reactive functional groups. In this study, the amino groups incorporated into the NMOFs were used to graft optical imaging contrast agents or platinum-containing chemotherapeutics. These modified NMOFs were coated in silica to reduce premature release of imaging contrast agents or chemotherapeutics before arriving at the tumor sites. Preliminary in vitro tests showed that these NMOFs could effectively cause cell death in human colon cancer cell cultures with an efficacy similar to cisplatin. The Lin Group hopes to further modify this strategy to deliver other cancer drugs and imaging contrast agents.
Published in JACS, the Murray Group reports how electrospray ionization triple-quadrupole mass spectrometry of ca. 1.6 nm diameter thiolate-protected gold nanoparticles has been achieved at higher resolution than in previous reports. The results reveal the presence of nanoparticles with formulas Au144L60 and Au146L59, present in the sample as a mixture.
The improved resolution is based on lowering m/z by exchanging multiple [−SC11H22N(CH2CH3)3+] ligands into the original [−S(CH2)5CH3] ligand shell. The nanoparticles are thus intrinsically cationized and appear as a series of 10+ to 15+ mass spectral peaks. The assigned state of charge was confirmed by a collision-induced dissociation measurement.