When an architect designs a building, core design principles like balance, proportion and symmetry are taken into consideration. But perhaps the most important consideration is functionality. What is the building designed for? What’s its purpose?  

These questions are similar to those asked by synthetic chemists when designing and building a new molecule through chemical synthesis.      

“Because we’re designing and building molecules at the molecular level, I like to think of us as molecular architects,” said Annaliese Franz, a professor in the Department of Chemistry at the College of Letters and Science at UC Davis. “We’re not just making something new. We’re designing it to have a specific function.” 

What does it mean to be a “molecular architect”? 

Franz and her team of molecular architects in the Franz Research Group are designing the future. Through organic synthesis and catalysis, the team is building and improving molecules with therapeutic potential. Some current projects include developing a new nanoparticle technology for livestock vaccines and improving treatments for neurodegenerative disorders like epilepsy. 

For Franz and her team, the periodic table of elements is akin to a LEGO set. These basic building blocks are key to next-generation therapeutics, but like any functional structure, the assembly is what matters.  

“From a simple set of building blocks, you can be creative about what you build, and you can make very complex structures,” Franz said. 

Why chemists think about molecules like LEGO sets 

Franz described both molecular design and LEGOs as having “infinite possibilities.” It’s an apt comparison. Both chemical synthesis and LEGO design have advanced considerably since their inception.  

Before advances in modern research, chemists didn’t have as many building blocks to use and mainly relied on heating (just like cooking) to cram building blocks together. This, according to Franz, was similar to classic LEGO sets, with the building blocks limited to bricks.  

More recently, LEGO introduced Technic sets with specialized building components — including gears, axles and beams — allowing models to be more complex and have improved function. For Franz, modern chemical synthesis — with new building blocks and advances in catalysis — is like a LEGO Technic set.         

“Our knowledge of chemical synthesis has evolved just like the creation of more advanced LEGOs,” Franz said. “When you have special building blocks, you can make more elaborate structures, with more interesting or more important functions.”        

Next-generation therapeutics harnessing silicon 

In research concerning the design and advancement of molecular therapeutics, Franz and her team have turned to silicon, the second most abundant element in the Earth’s crust, to create new building blocks. They’re strategically placing the element into a molecular scaffold in place of carbon, which has historically been used for drug design.  

“Silicon sits just below carbon on the periodic table and I like to think of it as ‘carbon’s inspirational cousin,’” Franz said. “It’s very similar in terms of the opportunities to build molecular architecture as part of the organic world, for drugs and materials.” 

While its similarities make it useful as a carbon replacement, silicon also possesses key differences that make it more attractive to incorporate into a scaffold for next-generation therapeutics. 

“The bond lengths are longer, and the reactivity is a little bit different, so we can access unique architectures,” Franz said. “The end structure looks very related to what you could have with carbon, but by adding a silicon, it changes the way in which you can connect the building blocks.”  

In essence, it allows for more efficient and sustainable synthesis of unique molecule structures with therapeutic potential. 

“In addition to the unique structure, we can also access improved function. Because of that, we have several projects where we are designing and building structures with these new silicon building block pieces,” Franz said.  

Engineering new lipids for next-generation therapeutic delivery 

In one project, Franz and colleagues conducted foundational research that improves the design of lipid nanoparticles with the potential to be used as a vaccine platform for livestock. The improvement, first reported in a study in ACS Applied Bio Materials, was achieved by engineering novel silyl lipids, which use silicon building blocks in addition to carbon in the molecular design.  

“Some lipid nanoparticles can have issues of stability,” said Franz, referencing hurdles to develop vaccine platforms. “There are challenges related to stability, efficiency of delivery and also the design of new targeted delivery areas”.    

“You don’t want a structure that is too stable, but you also don’t want it to fall apart too quickly, and ideally we want to be able to store therapeutics at room temperature, instead of requiring cold storage,” she added.  

To bridge the gap between the team’s foundational science funded by the National Institutes of Health (NIH) and future commercialization of a new lipid vaccine platform, Franz was awarded a STAIR grant totaling $75,000 in early 2025. The team is currently performing experiments in mice to study the safety and biodistribution of this silyl lipid-based nanoparticle technology.  

“We’ve done the synthesis of the new building blocks, we’ve evaluated the biophysical properties of the nanoparticles, and now we’re getting ready to do mouse studies based on the key results from cell-based work,” Franz said.   

Enhancing cannabinoids for epilepsy and neurodegenerative disorders

The team is also using new silicon building blocks in a project aimed at enhancing the potency of cannabinoids, a promising class of molecule for treating neurogenerative disorders such as epilepsy. Franz, who is also an affiliate of the UC Davis Institute for Psychedelics and Neurotherapeutics, won a 2023 Dr. Moshen Najafi Research Award in Medicinal Chemistry related to this research.    

“Cannabinoids are naturally occurring compounds with therapeutic benefit, but they are not that potent for some of the health effects that we want them to have,” Franz said. “There are known challenges associated with increasing potency.”  

Typically, cannabinoids target two receptors in the human endocannabinoid system called CB1 and CB2. The CB1 receptor is associated with the drug’s psychoactive effects while CB2 activation is associated with beneficial neurotherapeutic effects.  

The team’s silyl cannabinoid structures are being designed to selectively target CB2 receptors and bypass CB1 receptors.  

“If we can enhance potency and selectivity, then you can have an improved drug with fewer side effects,” Franz said.  

The team is working with colleagues at UC San Francisco to test their silyl cannabinoids in animal models, specifically zebrafish.  

“I think it is amazing that there is a zebrafish model that’s used to study seizure activity,” Franz said.   

The power of collaboration for translational science 

Franz emphasized that the research in her lab is a collective endeavor, one that’s not possible without students and collaborators who all bring unique ideas and contributions to the science.  

“It’s always powerful to have collaborations across the University of California system,” she added. “We have opportunities to work with experts in different areas so we can design and build new molecules to do translational science that impacts human health and society.”

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