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A Computational Analysis of Electrostatic Potential in Humulone, Cohumulone, and Adhumulone

In this experiment, I will be looking at the electrostatic potential of these alpha acids, which are present in hops. This will be done using WebMo. In my chromatographic experiments, cohumulone elutes alone, while humulone and adhumulone elute together in one peak. My hypothesis is that humulone and adhumulone will have similar electrostatic maps, displaying the similarity in their polarities (the reason they would elute together).

HPLC Trace

This image shows the elution of the molecules. The first line shows all of the peaks in one of my experiments. The first peak is cohumulone, while the second is the adhumulone and humulone. Please refrain from looking into peaks 3 and 4, these are the beta acids and do not pertain to this exact discussion. It should be noted that this exact experiment could be ran for the beta acids (lupulone, colupulone, and adlupulone).

Why Alpha Acids?

These alpha acids are integral in the beer brewing process. By adding hops (and thus the acids), you are able to introduce the bitter flavor that is prevalent in many types of beer. However, beyond this, alpha acids have antibacterial and antimicrobial properties. They also have the potential to be used in the treatment of different types of cancers, through the regulation of genes that can cause cancer when improperly regulated.

Structures of Humulone, Cohumulone, and Adhumulone

Humulone	Cohumulone	Adhumulone

The structures of these three alpha acids are incredibly similar. The only difference is an alkyl substituent change is the top right of the molecule. We are setting out to determine if this substituent change will lead to a change in the electrostatic potential of the molecules.

Electrostatic Potential Maps of Humulone, Cohumulone, and Adhumulone

Humulone	Cohumulone	Adhumulone

Here we see the electrostatic potential maps of the three compounds. It should be noted that these maps are not of the exact molecules. The large alkyl substituents off of the center ring were removed, as we decided that these would not play an integral role in the electrostatic potential of the molecule and remained the same in each molecule. In Flash Chromatography (reverse phase, C-18 columns), cohumulone separates independently, but adhumulone and humulone do not separate from each other. Instead, they elute in the same peak. Based on our electrostatic maps, this seems suprising. The humulone and cohumulone maps appear to be more similar than humulone and adhumulone. The cohumulone has more electrostaic potential on the oxygen near the top right of the molecule, while the other two do not exhibit this. One would assume that the polarity of the cohumulone and humulone would be more similar due to this, but this does not appear to be the case. Overall, this experiment did not provide positive results for the hypothesis, and further calculations would need to be performed to understand this phenomenon.

Electrostatic Potential Map of Full Molecule of Humulone

Humulone

Here we see the electrostatic potential map of the full humulone molecule. This could provide the start of further inquiries into this topic, as it could be compared to the full molecules of adhumulone and cohumulone.