The Solution is Salty

I’ve recently had an article, “The Electrostatic Origins of Specific Ion Effects: Quantifying the Hofmeister Series for Anions” accepted in Chemical Science (K. Gregory, E. Wanless, G. B. Webber, V. S. J. Craig and A. Page, Chem. Sci., 2021, DOI: 10.1039/D1SC03568A). I thought this presented an opportunity to challenge myself by writing about the article with less scientific jargon.

This work investigates specific ion effects. You may be surprised at how much you already know about specific ion effects. Have you ever asked someone to pass you the salt? Table salt is also known as sodium chloride and is made up of sodium cations (these are positively charged ions) and chloride anions (these are negatively charged ions). There are potentially millions of other salts and you might know these as minerals or electrolytes. For example, calcium salts are good for your bones, lithium-ions are common in batteries, and magnesium ions in sports drinks can help prevent cramps (these are all positively charged examples). In terms of anions (the negatively charged ions), fluoride is used in toothpaste, iodide for treating hypo/hyperthyroidism and acetate is a key component in vinegar. Each of these have very different applications and are examples of specific ion effects (where the effect depends on the identity of the ion).

The discovery of these specific ion effects is often attributed to Franz Hofmeister and his student, Siegmund Lewith, back in the late 1880s. Despite some forms of specific ion effects already being used previously throughout history, this was perhaps the first systematic study of these effects and inherently found some qualitative (by order) commonality between a few varied experiments (for example, they examined a few systems, including the precipitation of egg white proteins (“room temperature cooking”) and blood serum).

In essence, we’ve known a bit about these systems for over 130 years. The trouble is, they’ve been challenging to model and therefore predict. We’ve seen some benefits of modelling recently to direct Governmental responses to COVID-19. However, no theoretical recipes were available that allow us to say, “I have a salt with cation X and anion Y, which I’m putting in a solution of water containing enzyme Z. This salt will change how fast that enzyme works by U %.”. Until now…

Well, that “Until now…” was partially to be dramatic, but in this scientific paper we begin to address this issue. One of the reasons the recipe doesn’t yet exist is because we also need the right ingredients, and by this I mean the properties of these systems. A few properties have been postulated before (one by us) but they don’t consistently match what is happening in experiments. One of these properties is the polarisability of an ion. Polarisability is analogous to how “balloon-like” or “bowling ball-like” a molecule or atom is. If something has a high polarisability, it can change the shape of its electron density to a larger extent (like a balloon) and if something has a low polarisability, it can’t really change its shape at all (like a bowling ball). This parameter, or ingredient, is reasonably useful until considering non-spherical ions (with more than one atom) such as acetate (the vinegar ion), which you could think of as a little like a balloon dog – it can change its shape a bit and it has an important shape to it. The trouble is, it acts like a bowling ball.

This got me thinking. The fundamental ingredient must have some similarity to the polarisability, but when considering ions like acetate, which have multiple atoms, the atoms that are going to “touch” the other component (such as an enzyme) are the most important to consider. This is where my quantum chemical calculations come into play. I won’t go into too much detail on quantum chemistry here, but I’ll explain some aspects relevant to this work.

Quantum chemistry is done via the Schrödinger equations on a computer (this is one of the big uses of supercomputers, and will be a large application of quantum computers). It allows us to see and calculate things that aren’t yet accessible via experiments. This includes things that are too small, too fast, or too contaminated. In my case, I wanted to: a) calculate the energies of ion interactions and break these down into the fundamental forces (e.g., electrostatics, exchange, induction/polarisation and dispersion, and variations of these) and; b) parameterise each atom separately, within molecules.

So, in part a) I found that electrostatics (the force that works when you rub a balloon against your jumper and then it sticks to the roof) seemed to be the key aspect that determined many ion interactions. I used this in part b) which centred around electrostatics and Coulomb’s Law. This is essentially the law that opposites attract (positive likes negative, negative likes positive), and that the closer the opposites are the greater the attraction. In equation form, E=k(q1q2/R), where E is the energy of interaction, k is a “constant”, q1 and q2 are the charges of points 1 and 2 respectively, and R is the separation distance.

I used a technique called DDEC6 (developed by T. Manz and N. Limas et al.10.1039/C6RA04656H) that allowed the values of q (the charges) to be calculated at every atom. For “touching” atoms, R can also be approximated by r1 + r2, the radius of the atoms 1 and 2, which can similarly be calculated. For negatively charged anions, the (radial) charge density (which I’ve called “sho”, ϸ, which can be a lot of fun (for me) for visual puns), q1/r1 is closely proportional to the more complete electrostatic energy as described by Coulomb’s Law, since (in a given system), q2 is a multiplicative constant and r2 is constant and comparatively small. This means we have a parameter that correlates with the electrostatic energy of these anions.

Of course, up until here, it’s theoretical. So the next step was to apply this parameter to various experiments to see if it correlated. This is the exciting part. It did. Time to ϸ off.

Now for a few examples.

Electrolyte properties: These are important as a baseline for more complex models, but are very relevant to industrial processes and battery functions.

Viruses: For the viral activity of the herpes simplex virus 1 (HSV-1) protease, human rhinovirus-14 and human immunodeficiency virus (HIV) protease, there was a strong relationship. Now hopefully I don’t butcher the biological interpretation of activity here, but this implies that, in the presence of some ions (or salts/minerals), you can speed up or slow down the rate these proteases work and therefore the resultant symptoms of that virus. I’ll put in a disclaimer here that this data is obtained in experimental conditions and that these ions may work in this manner generally in the body, so there will be various other enzymes and proteins affected simultaneously and therefore there is potentional for various side effects. I’ll probably have to leave this with the biochemists and medical researchers to most beneficially use this information.

Stimuli-responsive systems: There are some large molecules that will change behaviour under certain conditions, such as light, temperature, or acidity. Light-responsive behaviour is already being incorporated into dual-functioning glasses/sunglasses. In the case of temperature-responsive molecules, salts can alter the temperature at which a change occurs, and this correlates with ϸ.

We also showed that when changing the liquid in which these effects take place, for example from water to alcohol (ethanol), certain properties of the liquid could account for this. A recent paper (10.1039/C9CP06800G) showed specific ion effects in the enzyme responsible for metabolising alcohol (and therefore a hangover). This might contribute to why sports drinks can help a hangover (they also help replenish sodium after depletion due to alcohol dehydrating effects).

When it comes to the cations (the positive component of salts) in otherwise uncontaminated water, the same electrostatic trends are observed. However, we also stipulated that in non-pure water systems (i.e., mixed with alcohol) other intermolecular forces come into play. For example, when a “tug-o-war” is occurring between the water and the alcohol molecules where the cation is the “middle of the rope”, the electrostatics (analogous to the anchor in the tug-o-war) have roughly equal strength on both the water and the alcohol teams. This means the differentiating factor can be one of the other team members, in this case, dispersion (similarities to gravity, often two large molecules/ions will have a stronger dispersion attraction than two small molecules/ions).


Understanding the origins of the specific ion effects that underpin our day to day lives allows for more control of ourselves and the surrounding environment. It’s like knowing the rules for a game. To truly master it, you need to know the rules, then be able to use them in conjunction to your advantage. It’s also a bit like having a road map that can help you reach your destination quicker because you know which routes are the shortest and straightest. Having the rulebook, or roadmap, of specific ion effects will expedite endeavours in multiple industries. Over 50% of all pharmaceutical drugs exist as salts, implying many initial drug discovery programs would benefit, accelerating the search for life-saving drugs in this trillion-dollar industry. Nutritional epidemiology studies the role of diet on health and disease. It is heavily reliant on statistics of the population, but the specific ion effect rulebook could help bring understanding to a personalised level. Additionally, with the emergence of smart solutions and surfaces, the ability to tune these via salt will broaden the scope of their applicability, whilst also informing us of similar mechanistic processes happening in our bodies. With the emergence of electric vehicles (EVs), the battery race is gaining speed (pun intended). These EVs are reliant on the battery (and/or capacitors, supercapacitors and fuel cell) technology to go the fastest, farthest and be the smallest, whilst charging quickly and repeatedly. Inherently, these are reliant on specific ion effects for optimising how much flowing charge you can pack in a small space. So they’re important for “bettery” development if you will. Finally, EVs are one of the combatants of climate change. Another combatant to global warming is the glaciers at the ice caps that reflect a lot of the suns radiation. And guess what… Their stability is also dependent on specific ion effects. As is the stability of soil that might determine its disposition to erosion.

So yes, specific ion effects affect almost all aspects of our lives, and while this study didn’t quite finish the specific ion effects rulebook, it did find a very important rule – The Electrostatic Origins of Specific Ion Effects.

— Kasimir Gregory

Research funded by an Australian Government Research Training Program (RTP) Scholarship and Australian Research Council funding (ARC DP190100788, LE170100032 (INTERSECT)).


3 – Distracted

I’ve found myself easily distracted as of late. Jumping on and off my phone. Scrolling social media mindlessly. A rapid succession, from one app to the next. Indecisiveness when choosing a leisure activity. Living in a state of hyperstimulation. Almost missing the privilege of boredom over the burden of infinite choice.

This perhaps came to a tipping point last night when I felt all too aware of my unsocial behaviour in the lounge room when a group of us were hanging out. I wasn’t quite present. It was enough of a self-realisation to do something about it.

I’ve been meaning to reignite my meditation habit. I’ve been suffering from a case of “but will it really make me feel any better”. Despite a great track record of it making me feel better, I somehow often manage to convince myself that it’s more effort than it’s worth. This same dilemma can appear in multiple facets of my life – exercise, diet, outdoors.

The one place I haven’t quite found that to be true, has been sleep. I know it should, and perhaps I just haven’t built the habits, but I can feel worse after 8+hrs than 5. I need to note – I’m basically always tired. I am most probably suffering from a mild form of sleep apnea due to a deviated septum and swollen turbinates. It is almost like always having a mildly blocked nose; breathing through a valve. Another way I’d describe breathing through my nose oftentimes is like this:

  • Place a hand over your mouth, with no space between your fingers.
  • Now let just enough air in through the gaps so you can breath, but not comfortably.

You can survive, but its not comfortable and not particularly relaxing. There is also a bit of day to day variability – similar to the different pressures that you might use with your hand in the above exercise.

Now, thankfully I can also breath through my mouth. I’m often a mouth breather. Yet, I daresay my quality of life is somewhat depleted by this and its affect on my sleep. Thankfully, I should be getting it fixed in a month and a half – so I’ll keep you posted for updates on that matter.

Anyway, that distraction to talk about sleep instead of distractions was relevant to my point about distractions. I find that when I am more tired I am also more easily distracted and less motivated. Basically every basic task feels harder.

This is where my meditation comes into play. I think the effects of poor sleep can snowball these mindless habits. However, I believe I can combat that with meditation. The act of mindfulness to sharpen the skill of focus. To ask myself, before I pick up my phone, the simple question. Why?

This simple question might be enough to realise I don’t have an answer. It was a habitual act. Yet, it doesn’t limit when there is an answer – “I need to call my parents.”, “I want to do my daily Japanese lesson.” and even “I have worked hard this morning – I have 5min still till my next meeting – I’ll see what’s going on in the news or stock market.”

I want to strive to do a meditation each day of August – I feel this is a good timestamp to get an idea as to where my heads at, so I can compare in a month. I started using the app “Waking Up” last night – so far I’m really liking it. I was previously using “Smiling Mind” – but I think I had just become too used to the 15min meditation that it was easier to tune out – and therefore felt less effective in helping guide me through a session.

Today I went orienteering. I drove the 30min there and back with no radio or music, and of course had nothing but a map for the 75min run. There is something incredibly freeing about it being just you and your thoughts. The mono-tasking felt good. I didn’t get bored in the absence of the stereo. I think I actually just found myself noticing more about my surroundings.

When I got home I had a shower and nap. Then I watch Vikings for a few episodes – I treated myself to relax. What was different to a lot of the time when I am watching TV, was I didn’t do anything else – except rehydrate. I focused on the show – and enjoyed it more. No computer. No phone. Just me, some water and the TV. Perhaps, counterproductive to limiting hyperstimulation, but I enjoyed my Sunday and taught myself a little about just enjoying what I’m doing.

Hopefully, I can write a piece in September called “Focused”. I’m looking forward to this self-experimental training block of using meditation as my “focus weights”, with “Waking Up – Sam Harris” as my coach.

Keep Anion The Future.


2 – Deliberate practice

I’ve recently been listening to the The Unmistakable Creative Podcast, which I have been thoroughly enjoying through it’s mix of stories by inspirational people and discussions about some really progressive technologies or concepts. It was listening to this podcast on a recent trip to Armidale that actually inspired me to start my own, as the host, Srinivas Rao, said something along the lines of “I really enjoy meeting people, so I decided to build a platform where I can do that”. I thought – what a great idea. I also like meeting people. I like talking about research. Why not have a go myself?

Now in the episode I am currently midway through, the interview is actually with Srini, where he is discussing his new book, An Audience Of One. This motivated me to write this blog post for two reasons. Firstly, to write it for myself. The second reason was due to the discussion on deliberate practice.

Deliberate practice is something I am diligent on in many aspects of my life – however my focuses can fluctuate. Currently, I am sitting on a 264 day streak for Japanese on Duolingo, a 53 day streak for brain training on the Peak app (although, I’m probably sitting on 363 of the past 365 days that I did it). I am on day 32 of a 16:8 intermittent fasting self-experiment (perhaps this could be a post in its own right). I had similar habits with meditation, although unfortunately that has fallen away a bit as it requires a very deliberate allocation of time for it. I had similar pedantic habits in 2011 and 2012 with my running training (although it was more of a do not miss a day of my training program – even if that meant resting).

Perhaps the point I’m coming to with all of this is, this particular blog post is a piece of deliberate practice for my writing. Not because I want to become a writer or a blogger, but because I want to improve my writing for when I need to do it – most notably for scientific journal articles. When I say I want to improve my writing, probably the quick assumption would jump to improvements in grammar, articulation, vocabulary. Sure, I would like these things to improve, but the real purpose is process. To remind myself that yes, I can write 500 words in 45min if I just let my thoughts flow from my head, down my arms and into my hands, where the fired neurons allow the click-click of my fingers against the keyboard.

It is somewhat a strange practice, writing this for myself, whilst it is accessible to anyone with an internet connection. However, it may still only be read by me. Perhaps this is a good test. If you are reading this, here is a message for you:

Hello! I hope you are having an excellent day. Feel free to leave a comment saying- “First!” You win. Unless there is already a comment saying “First!” In which case, “Second!” You were so close! Unless there is already a comment saying “Second!” In which case, this really blew up didn’t it. If it gets to that many comments, I’ll allow free reign of the corrections to my grammar (not that anyone really requires permission), but perhaps I can learn a thing or two from this deliberate practice. Alternatively – leave me a challenge topic to write about for my next deliberate practice of writing.

Good day, enjoy the multifarious thoughts, and keep anion the future.


1 – Testing out the Blog

What is a blog? Is it the journal of our age? Where we put our thoughts – yet instead of it being a personal and private experience, it is instead very public and extrinsic. Although in this particular case – it is probably quite private, given the lack of publicity this website currently has. Which I am thankful for, for the time being. Less pressure to have a sufficient level of grammar to survive the online slander that may inherently occur in line with more views on the writing. Less exposure to the judgement of others, and therefore less of a requirement to adhere to my occasional perfectionist tendencies.

I suppose right now I am testing it out as a brain dump – trying to see where everything will be posted on my website and how I might need to clean everything up to have it more organised and easier to navigate. I sit here wondering – will this be the only post I do? Or, will I decide to write about my interests?

Perhaps an internal discussion about my thoughts on the brain and neurochemistry could be one topic. For example, one thought is – with sufficiently accurate brain scanning technology, could you effectively read someones mind? Could you use electrodes to stimulate someones mind? Such that they were experiencing what you wanted them to – which is an exciting and terrifying thought. Exciting in the sense that you could have new age movies that were instead experienced. Perhaps, empathy could be reached from a literal sense if you could actually experience walking in someone else shoes. Terrifying, by the same measures. Firstly, a malicious person could make you experience a torturous event (my mind goes to an Altered Carbon scene). Secondly, would we have a problem of not knowing what is real (here I think of inception)?

Now, I’ve already diverted my thoughts along this railway, and it begs the very philosophical questions. If that technology were possible, how do I know I’m not already experiencing it? If I was experiencing it, would it even really matter – it feels real to me? How could I test if it were real? What kind of laws would need to be put into place with this technology? Would it be something humanity achieves and then realises its not something to be used? Much like the atomic bomb. Or, would the subtle nature of its encroachment into society ensure we don’t realise what we’re doing, like the frog in boiling water fable (even if this fable isn’t inherently based on truth – the message itself might).

Okay, now I switched thought trains because of the frog fable and as to whether there are any stories that might replace this, and whether it is based on psychological reasons. Maybe I can check for papers on the topic. But does can it derive from over investment in a situation, shares or project because of not wanting to waste an initial investment, so a doubling down ensues.

Time to wrap this up. Despite my tendency to feel like I’ve always got to write at least X amount – perhaps I can practice holding back here, and only write (X-1) amounts. So, I’ll stop my procrastination now and write the little bit of python code that I need to in order to do a batch analysis of radial distribution functions. I’d prefer to automate the process than do over 1000 myself.

Good day, enjoy the multifarious thoughts, and keep anion the future.