The results will help researchers screen and optimise such molecules for new applications such as mRNA vaccines. The project built on a collaboration between the ISIS deuteration facility and the deuteration lab at the JCNS.
From soaps to pesticides
Surfactants are everywhere, from soaps to household cleaners, fabric softeners to pesticides. Their ubiquity and usefulness are a result of their particular molecular structure; a hydrophilic head perched on a hydrophobic tail. That structure lets them bind to both water and grime, making them effective cleaning agents and soaps. The head group can also carry a charge, imbuing them with other useful properties.
For instance, cationic surfactants have a positive charge on the head. That makes them particularly useful as fabric softeners. It also means they are effective antimicrobials as the positive charge is attracted to negatively charged bacterial cell membranes. The hydrophobic tails then penetrate the bacterial membrane, leading to cell death. However, the positive charge means they are less effective cleaners than nonionic surfactants.
To overcome that limitation, cleaning products often use a mixture of nonionic and cationic surfactants. That can cause further issues, however, as nonionic surfactants can interfere with the cationic surfactants' antimicrobial properties. The question for researchers is whether it is possible to optimise cationic surfactants to overcome these limitations by altering their molecular structure?
“A huge project"
To address that challenge, the researchers created a novel range of nonionic and cationic surfactants in which they could adjust key properties by altering the length of the hydrophobic chains that make up the tails, and by changing the number of ethylene oxide groups on the head, which also increased the size of the headgroup. Increasing tail length makes the surfactant more hydrophobic, while increasing ethoxylation of the head makes it more hydrophilic.
To investigate how these changes affected the behaviour of the surfactants, Yao Chen and colleagues in the ISIS deuteration facility had to synthesise the molecules, incorporating deuterium instead of hydrogen in their structure. That allows the molecules to be “seen" by the neutron beam they are exposed to and increases the contrast, providing the researchers with more information about the molecules. This was the first time anyone had deuterated these molecules, with the ISIS deuteration facility team leading the effort and receiving technical support on ethoxylation methods from JCNS.
“This was a huge project," says Chen. “We created 48 compounds over two years."
Optimising for new applications
Once they had synthesised the surfactant molecules, the team used a combination of three ISIS instruments to study their behaviour.
The researchers were interested in how their changes to the surfactants altered their behaviour in two environments; at the air-water interface and suspended in solution.
To study their behaviour at the interface, the researchers used neutron reflectivity on the INTER instrument. They found that both nonionic and cationic surfactants with longer chains were less densely packed at the surface, despite previous studies showing chain length had no effect on packing. The addition of ethyl oxide groups to the headgroup reduced packing density, as expected.
The results also showed that the cationic surfactants were either similarly or more densely packed than the nonionic surfactants, which was surprising; the researchers expected repulsion between the positively charged heads to make it more difficult to pack the molecules close together. Their conclusion was that the ethylene oxide molecules shielded the positive charges and altered the way the molecules packed together.
In solution, the surfactants self-assemble into structures called micelles, where the molecules arrange themselves with hydrophobic tails pointing inwards. The researchers used small angle neutron scattering on the SANS2D and LARMOR instruments at ISIS to investigate the differences between the micelles when comparing the nonionic and cationic surfactants.
For both, larger headgroups meant smaller micelles as the curvature of the surface increased. Longer tails also resulted in larger micelles. Cationic surfactants formed smaller micelles as the positively charged headgroups repelled one another and ethoxylation meant the molecules packed together differently. The researchers also found stronger interactions between the micelles due to the positive charges.
The results show that cationic surfactants can be created and optimised for specific purposes, paving the way for new applications. This could include, for instance, using ethoxylated cationic nanoparticles in new mRNA-based vaccines.
Read the full paper here: https://doi.org/10.1016/j.jcis.2024.06.174
