Surgical Serums

 

Here comes the sleepy juice” said the anaesthetist as he prepped me for surgery and injected me full of a milky looking blend to make sure I couldn’t see, hear or feel anything that would happen over the course of the next two hours. As a scientist I couldn’t help but wonder what exactly the ‘sleepy juice‘ was, but I had passed out before I was able to form this question out loud.

Intravenous anaesthesia is often made up of a cocktail of different substances, each with their own specific purpose. The active component of the milky concoction was likely to be a molecule called propofol whose job is to induce amnesia and ensure that there is no memory of the period of time that propofol is in the body. It usually comes as a mixture of 1% propofol and 10% soybean oil. The rest of the components include egg phospholipid as an emulsifier, glycerol as a tonicity-adjusting agent (to balance osmotic pressure), and aqueous sodium hydroxide to adjust the pH. It is believed to interact with the GABAA receptor – a ligand gated ion channel found in nerve cells that is involved in virtually all brain functions. The inhibitory action of propofol drastically slows the progression of signals through the nervous system meaning that the patient is not be able to think, create any memories, move, or see or hear anything. Most importantly they are not able to feel any pain during the operation! Incidentally, propofol was the drug allegedly used to kill Michael Jackson.

Propofolpng

The chemical structure of propofol

The levels of anaesthesia in the body is closely monitored by specialists called anaesthetists whose job is to make sure the anaesthetics don’t wear off during the procedure. In general the duration of action of intravenous anaesthetics is between 5 and 10 minutes after which the patient will spontaneously regain consciousness. To stop this from happening the level of anaesthetic in the body is maintained, either by via a suspension of propofol in a drip that enters the body through an intravenous catheter, or by the inhalation of a gaseous anaesthetic such as sevoflurane (so named due to its highly fluorinated structure). Historically, volatile solvents such as chloroform and diethyl ether have been used as anaesthetics, which can explain why you might feel a little light headed after mistakenly inhaling too much during a day in the organic teaching labs!

Sevoflurane

The chemical structure of sevoflurane

*This article will also appear in the autumn semester edition of ‘Resonance,’ the University of Sheffield Chemistry Departmental magazine.

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What do YOU think??

This week the Royal Society of Chemistry (RSC) published the results of a study with regards to the public perception of chemistry, chemists and chemicals. To me the results seem to indicate that the public perception of our field is improving and fewer people are still scared of hearing that some product they use ‘contains chemicals’.

One of the more interesting results for me were the ones in blue at the top of the infographic below (click to enlarge). They seemed to imply that the public perceive chemists and chemistry as important but that chemists did not think this would be the case. There may well be a major lack of self-esteem amongst chemists, but this may also be an artefact of the times when ‘chemist’ and ‘pharmacist’ were used interchangeably.

Either way, the outlook seems good to me. Do you agree with the results? Let me know in the comments below.

public-attitudes-to-chemistry-infographic

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Post Race Blues

Sorry if you were expecting some science – I do have a couple of posts lined up, I just need to get around to writing them! In this post I want to get something off my chest that really affected my life over the course of the last few months. This is going to be somewhat of an emotional outpour than anything else that I’m too uncomfortable to talk about in real life…

As you may or may not know, I completed the Berlin Marathon at the end of September 2014. Despite persistent and crippling calf craps after the half way point, I actually managed to get around the course in an OK time (for a first-timer at least)! The feeling I had at the finish line was an very bizarre mix of relief, happiness and self-loathing for allowing myself to participate in anything that could cause so much pain!

741910-1169-0005s   741875-1032-0048s

As you might imagine, after the race the thought of even moving at any pace faster than walking was VERY unappealing. So I just forwent exercise in any form. I was happy in doing this for a short while, but it very quickly became apparent to me that something was wrong. I started to feel disgusted with myself and the way I was living, but my laziness meant that I’d gotten out of shape and this made me feel scared about staring to run again. I had put on a lot of weight and was out of shape so didn’t have any motivation to run, so I got more out of shape and less fit as the weeks went on, trapped in a vicious cycle of self-deprecation and disappointment.

Thankfully, my research seemed to be at some kind of high point where lots of things were working and I was getting some good results. This may have been the one thing that kept me going – by working long hours and entirely focussing on chemistry I was able to forget about the negative thoughts I’d developed about my lifestyle at the time, but the people around me had started to notice that I “wasn’t being myself” and constantly asking if I was OK.

I’m generally not the type of person to openly express my feelings and was in denial, insistent to my friends and coworkers that I was “fine” and that I didn’t need their help. During this time I was doing a lot of self-reflection and started to make some changes. I deleted Facebook after realising that almost everything that came up on my feed was utter rubbish and that I didn’t care about it. I elected not to celebrate my birthday after realising that there is literally no point. In previous years I never got any meaningful presents and the cards always went straight in the bin. I hated the attention it generated and the horrible questions of people wanting to know what you got and what you did which always to me just seems nosey or fake. Besides this, given the way I was feeling at the time I didn’t feel it was appropriate for anyone to have any sort of celebration in my name. But despite these, and some other changes I still felt awful.

One day I finally broke. Someone asked if I was OK and it dawned on my that I really wasn’t. I couldn’t even answer. I had to leave work, get a friend and go to a cafe where I just unloaded everything that I’d been feeling since the race and fully broke down. I felt like an idiot, sat in the middle of a cafe bawling my eyes out on my friend but I just couldn’t stop. She kept asking me what had made me so upset but no matter how hard I tried I couldn’t put my finger on it. I felt like shit (excuse the language) but had no idea why so couldn’t do anything about it. When I eventually stopped crying we talked things through and it pretty much came down to the fact that I’d stopped exercising and was working such long hours that I had no time to see my friends.

I never actually believed in the runners’ high. Whenever I finished a moderately distanced run I was exhausted, shaky and felt a bit sick. I thought the supposed high was a myth, or that I just wasn’t affected by it, but the lack of endorphins pumping through my nervous system when I stopped running regularly obviously caused my body to go into some sort of ‘depression mode’ if that exists, and it kind of explained how unhappy I’d felt over the previous months. I realised I would have to start doing some sort of exercise again, and much as the thought of running again was scary, I knew it was what I had to do to make myself better.

In that cafe, I resolved to do two things:

  • Start running again
  • Make more effort to make time to see my friends

The latter was easy. At least once every couple of weeks we’d meet up and have dinner at someone’s house. Although I see most of my friends at work every day, we’re ultimately still at work and people have other things on their minds. This was an opportunity to see the people closest to me in a different setting and I found that this put me in a much better (and healthier) mental space. Despite this though, my body was in a state. I’d put on about 15 kg (30 lbs) since the marathon and was out of breath after just walking up the hill on the way home from work.

With no goal I was struggling to find the motivation to do any running so I did the unthinkable and signed up for another marathon. After paying my race entry fees and going on my first run since Berlin, it became very clear to me that a lot of work needed to be done to get around this one and this is really helped to motivate me to try to get my fitness levels back up to where the had been last year.

I am now in a much happier and healthier place and look back on the last few months as almost hilarious! To have gotten myself into such a state over something that was solved so easily is pretty laughable! I will forever be indebted to the friend who took me to the cafe, though. She is one of the few people I consider as a true friend with whom I can be completely open without worry of judgement or her telling people what I tell her and I truly hope she feels the same about me.

If you’ve made it this far, thanks for reading! Sorry for all the emotions, but it’s something I really needed to get off my chest. I assure you that most, if not all, future posts will again be about science and how chemistry can affect our lives and the world around us. Until next time!

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STORM

The Nobel Prize for chemistry in 2014 was awarded to the scientists who developed stochastic optical reconstruction microscopy, or STORM for short. But what does all of that even mean?

STORM is a type of microscopy that enables the visualisation of structures in, for example, animal or bacterial cells with resolutions up to ten times better than when using a conventional microscope. Think about the difference between the camera phone you had ten years ago and the camera on modern day smart phones! The image below demonstrates this difference in resolution when imaging biological samples.

The techniques works by exploiting fluorescent dyes (molecules that give out light) that are able to blink on and off. After attaching the dye specifically to one cellular component, a video can be taken of the dyes stochastically (randomly) blinking. This video is then fed to a computer program that isolates each molecule in each frame before finally reconstructing a super-resolution image, as shown below.

STORM vs microscopy

But so what?!? Why is this so much better than the other techniques out there? It’s because optical microscopy doesn’t damage a sample! The other ways of imaging at this resolution (such as electron microscopy or near-field microscopy) can damage the sample or be operationally difficult.  STORM can be used in a way that doesn’t damage a sample AND is easy to operate – believe me, I’ve tried it!

“This sounds great! But what makes the dyes blink?” I hear you ask? Well actually no one knows… This is where I come in! My PhD project is based around making small changes to fluorescent molecules using synthetic chemistry to test how this affects the “STORM-ability” of the dyes and trying to pinpoint certain qualities required for blinking.

Maybe down the line there will be a Nobel Prize for me too! For now though, I will leave you with a couple of pictures of my colourful compounds 🙂

IMG_0572 IMG_0588

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Now you see me!

There once was a time, long ago, when I was told that “atoms are the smallest things in the world, and we will never be able to see them.” Who knew then that science would advance to such an extent that not only can we distinguish atoms, but can detect intermolecular interactions and observe chemical reactions as they happen!

These discoveries have all been made possible by the advancement of a technology called atomic force microscopy (AFM). This is a technique where a cantilever taps a surface as it sweeps over it, feeding back information about how far the lever has to dip in order to touch the said surface, enabling the user to create a 3D map of the sample. For a more detailed explanation of how AFM works, have a look at the first few slides of this animated slide show: http://www.parkafm.com/AFM_guide/how_afm_works.php

Strands of DNA on a surface captured using AFM

For a number of years, AFM has been used to capture images of things like strands of DNA on a surface, as shown above. This year, however, there have been significant advancements in the field that have allowed us to see much, much more. Not only is it now possible to see bonds between individual atoms in molecules, but an actual chemical reaction has been observed!

atomic force microscope images

Images taken using a microscope (top) and AFM (middle), compared to their molecular structure diagrams (bottom)

The picture above shows snapshots of a chemical before and after it has been chemically transformed. There are some red/yellow blurs taken using a microscope and it’s fair to say that you can’t really tell what they are. In the middle images taken using AFM, however, it is much easier to distinguish the structures of the molecules – they even resemble the drawn representations that scientists typically use to draw molecules! As a scientist and a chemist, this is hugely exciting. Who knows what the future of AFM could be? Maybe we might one day be able to observe reactions in real-time, and conventional methods of characterisation like NMR (which is presently the instrument that can tell you the most about what your molecule looks like) might one day become obsolete?

That research was published in May of this year, and yesterday even more astonishing research was published. The image below shows four molecules interacting with each other using hydrogen bonds. Hydrogen bonds are one of, if not the most important intermolecular interaction. They water its unusual properties, they hold together our double stranded DNA helices, they reinforce fibres such as nylon, as well as many other things; but they have never been witnessed until now (because they are much less strong than actual chemical bonds).

An AFM image (left) of four molecules(8-hydroxyquinoline) hydrogen bonding with each other, compared to another representation used by chemists to draw molecules. Grey = carbon, white = hydrogen, blue = nitrogen, red = oxygen, dotted line = hydrogen bond.

This is, again, a massive breakthrough for science. Being able to see the ways in which molecules interact with each other could not only give us information about how some chemical reactions proceed, but why they proceed in that way.

All in all, this research leaves me very excited about where science can go, the amount of power a chemist may one day have to analyse molecules, and in eager anticipation of the day I get to use an AFM machine and see an atom or molecule for myself.

For more science blogs across different disciplines, go to http://www.sciencebrainwaves.com

References:
Science, 340 (2013), 1434-1437 (DOI: 10.1126/science.1238187)
Science (DOI: 10.1126/science.1242603)

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Teaching old drugs new tricks

Thalidomide. If you studied chemistry to A level you will know that this is the name of a drug which was once prescribed as a sedative and to pregnant women to prevent morning sickness in the 1950s. It was, however, banned for use because of a property of thalidomide that was, at the time, overlooked – its stereochemistry (the way its atoms are arranged in 3D space).

The chemical structure of Thalidomide. For those unfamiliar with stick drawings, every corner is a carbon.

The image above shows thalidomide’s structure. The wiggly line between the carbon on the 6-membered ring and the nitrogen on the 5-membered ring indicates that there are two ways to arrange the molecule in 3D space, i.e. if the 5-membered ring is in the plane of your computer screen, the 6-membered ring could either be seen to be angled into or out of the screen. It was discovered that one of these arrangements was responsible for birth defects amongst children whose mother had taken the drug during pregnancy.

BUT it has recently been discovered that combining thalidomide with a yellow pigment from turmeric (curcumin) produces a molecule which can kill multiple myeloma cells – the second most common blood cancer! The curcumin section (which also shows anti-cancer properties) ensures that the thalidomide section doesn’t degrade in the body, and the thalidomide section makes the curcumin section more water soluble. The hybrid compound has higher toxicity against cancer cells than thalidomide or curcumin alone or any combination of the two.

The new hybrid compounds have not yet reached human clinical trials,  but have shown promising activity against myeloma and prostate cancer in animal models.

One of the cucumin-thalidomide hybrids which have shown promising anticancer results

One of the cucumin-thalidomide hybrids which has shown promising anticancer results

Reference: Org. Biomol. Chem., 2013, 11, 4757-4763. DOI: 10.1039/C3OB40595H

For more science blogs, head to http://www.sciencebrainwaves.com/

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Golden Balls

Can’t find your condom? No problem! Researchers in China have developed a new type of contraceptive! All you need to do is inject your testicles with gold nanorods and irradiate them with infrared light… Sounds pleasant!

The treatment works in a similar way to your microwave. A microwave works by using radiation of a certain frequency to make the water molecules in your food vibrate and generate heat. Infrared radiation would cause the ‘hairs’ on the nanorods vibrate, producing enough heat to kill off our little soldiers (if you know what I mean!) and the cells in the glands that produce them.

nanorods

Rod shaped gold particles covered in ‘hairs’ which vibrate when exposed to infrared light

Research has only been carried out so far on mice, but there are plans to extend the treatment into the canine and feline worlds as an alternative to surgical neutering. There are talks, however, of one day applying the treatment to humans!

With a shorter exposure to infrared light, it is possible to ensure that the testes’ temperature doesn’t climb too high, and that the infertility would only be temporary – a week or so. The paper seems to imply that this could be an alternative to using condoms, but I personally doubt that it will catch on – what sane man would let anyone go near his gonads with a needle!

Reference: Wen-qing Li et al., Nano Letters, 13 (6), p2477 (DOI: 10.1021/nl400536d)

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