PhD Update: 2019 Q2

It is now the end of June, so its time to reflect on the second quarter of the last year of my PhD. Did I achieve everything I set out to do? Read on to find out…

I did manage to send away the set of compounds I was talking about last quarter – the ones that would define the end of two results chapters of my thesis and the chemistry I plan to do for the rest of the year. I’ve received half of the data back about them, and it seems my compounds made by the shorter chemical route seem to work about as well as the ones made by a longer route.

Unfortunately, I don’t have all the data back. I don’t have the information about a potential side effect my drugs might cause. This side effect may be caused by my drug fitting into an enzyme that’s very similar in shape to the one I specifically want to investigate with my drugs. I need that “selectivity” ratio (i.e. how well the drug shuts down one enzyme vs another) to be better than my best compound so far (it’s a 7-fold different at the moment) otherwise I’ll need to go back to my old chemistry which took a lot longer to carry out.

 

cauldron
Image caption: Fiona standing in front of a giant cauldron at Warner Bros Studios: The Making of Harry Potter. As a chemist, I couldn’t resist posing by this potions staple! 

 

Usually, I get both sets of data at the same time, but my collaborator has been having issues with setting up the “side effect” experiment, which is unfortunate timing, but these things happen. Hopefully, she’ll have managed it before the start of next month. Otherwise, I can either send the compounds to a company to run the same test or make a guess and get on with the faster and easier chemistry in the process. My current “to make” list seems to have a lot of easy-to-make compounds that don’t seem to have been made before, so there is value in making them despite not having all the information I need to justify making them over other compounds.

I mentioned I’ve made some of the compounds that will wind up other chapters of my thesis. There were two on the list that I have been struggling to make for a very long time. It’s got to the point where I’ve put a pin in those for now, so I can focus on trying new things. After several months of trying to make the same compounds, I’ve had enough. It may well be that with current chemistry techniques and reactions, it isn’t possible to make the particular molecules which I have in mind – which is still new to the field.

I have written up these two sections of my project in paper form for the last month or so and once I get some repeat experiments run by my collaborator I should be able to submit those papers to journals and hopefully get that chunk of work out there – even if it wasn’t successful, I’ve still made some brand new compounds that don’t seem to have been made before which someone else could apply to a different project. This is the first time I’ve tried writing papers and the words have come relatively quickly, which I think is thanks to me spending a lot of time writing as a theatre critic/interviewer in my spare time. Keep those hobbies up, you never know where those transferable skills might come in handy.

I also received some bonus good news regarding papers: I found out some compounds I made in 2015/2016 as part of my master’s project are being included in an article so I might get another publication to my name as well! That project shows how long it can take to discover new things in the early stages of drug discovery. I made that compound 3 years ago, and it’s only now that the biologist I made it for has a nice rounded research “story” to share with the world.

In terms of science communication stuff, I really enjoyed taking part in Soapbox Science Brighton. I got to stand on a soapbox on Brighton beach and share the similarities I’ve found between baking and medicinal chemistry. It was a lot of fun to speak about science in such a unique space!

 

soapbox
Image caption: Fiona standing on a soapbox by Brighton beach in a lab coat and holding a massive cake as part of Soapbox Science Brighton talking to a crowd

 

I tried out that talk for the first time at another event called PubhD in Hackey, London and led other drug design workshops at Sussex University and the London Science Museum. I’m doing well at keeping the science communication stuff to weekends or short periods on campus so I can get on with other work – I’m usually far too good at saying yes to distractions.

 

pubhd
Image caption: Fiona talking to a crowd in a pub at PubhD London

 

I visited another conference, a longer one this time in Ghent, Belgium. It was called Bioheterocycles 2019. I got to give a 15-minute talk about my project which seemed to be well received and enjoyed the mixed programme of interesting chemistry talks and social events including a boat tour, banquet and Belgian beer reception.

 

ghent
Image caption: Smiling selfie of Fiona in the medieval city of Ghent in Belgium

 

Non-science stuff included playing in orchestras for some concerts in the Albert Hall in London and the Usher Hall in Edinburgh; I’ve moved to a flat of my own for the last six months of my PhD and I enjoyed a trip to Warner Bros Studios and a little holiday to Centerparcs to celebrate my partner Darren having his birthday and passing his thesis defence – I’m very proud of him and hope to be in the same position as him by this time next year!

Over the next three months I aim to submit those two papers; have a productive couple of months in the lab making some finer tweaks to my best compound to make it even better; as always, get up to date with my data analysis and experimental write-up; do some theatre reviewing at the Edinburgh Fringe in August and attend another conference in Athens in September which I have just secured a grant to attend. This is the beginning of the end!

How have the past few months been for you? Do you have plans over the summer? Let me know in the comments below.

 

What’s In My Fume Hood?

This is the 2nd post in a series of showing how I work. Today I’ll show you around my fume hood. A fume hood is a ventilated cabinet with a retractable hood where I carry out most of my chemistry to reduce my exposure to chemical fumes.

labelled fume hood
Picture caption: fume hood containing various pieces of lab equipment. Adjustable glass front, a bit like a pull-down blind.

Sometimes you have a to share a fume hood with another chemist if there’s a shortage of space but I’m lucky enough to have whole fume hood to myself in this lab, especially as this one isn’t very big. In my undergraduate studies, I was usually sharing with one or two other chemists in larger hoods – it was a bit of a squeeze! My fume hood on placement ran up to the ceiling so I could actually stand up inside it when I cleaned it at the end of my placement year, which was a rather surreal experience!

On the side of each hood are various taps for various things. One is for water, while others provide a flow of compressed gas or nitrogen gas when I need them. When reactions need to be run under unreactive conditions are stirred under a constant flow of nitrogen gas, or another unreactive/inert gas like argon to stop the usual reactive oxygen and water vapour from reacting with the chemicals.

The brown bottle, or “Winchester” as these 2.5 L glass bottles are known, is a recycled solvent bottle where I put my solvent waste. Liquid chemicals that I am finished with are poured into these bottles and once full, disposed of by our technical services.

Chemical waste in organic labs is typically separated into two classes – halogenated and non-halogenated waste – but this can vary depending on the contract a lab has with a waste disposal company. Halogenated or non-halogenated refers to group 17 of the periodic table, the halogens (chlorine, fluorine, bromine, iodine, etc.) and essentially if the major component of the reaction mixture contains one of these elements, it needs to go in the “halogenated” waste while anything without those elements goes in the “non-halogenous” waste. The reason they are separated is that combination of some halogenated and non-halogenated species, e.g. acetone (CH3COCH3) and dichloromethane (CH2Cl2) results in a chemical reaction! It’s very important to keep your waste separate.

The efficiency of a reaction can be measured in terms of how much product you get relative to the amount you calculated from the starting material, expressed as a percentage yield, but increasingly, in terms of how much waste is produced per g of material. Some reactions create very little waste but sometimes I can fill a Winchester of waste in a day if I’m running a  lot of purifications which use lots of solvents.

I have a yellow and orange sharps bin for disposing of any sharp needles I use in my reactions. Syringes are frequently used to add precise quantities of a liquid reagent to a reaction mixture.

The metal bars are used to clamp different pieces of glassware in place using all manner of knobs and handles. I like to have a portable clamp stand in my hood because my hood has fewer bars than some of my colleagues.

Any sample vials I have in my hood typically have a final product in them that I’m waiting to dry. The constant extractor fan that’s running makes it useful to transfer chemical products by dissolving them in a volatile solvent that evaporates easily. Once dry I transfer lidded samples to my bench.

Ongoing reactions tend to be in various round-bottomed flasks (RBFs). RBFs, as the name would suggest are spherical pieces of glassware with different fixtures to connect with different lab apparatus. TO hold them upright I use cork rings, made of actual cork or plastic, to store them in the hood. I typically have more than these in my hood but this was my “tidy hood” before Christmas.

Picture caption: hot plate with glass reaction vials above it. Magnetic pellet in mixture to aid stirring

When reactions need to be heated I typically use a magnetic hotplate stirrer like these two in my hood. The hotplates work very similarly to the ones used in cooking and have dials to control temperature and extent of stirring. I stir my reactions by adding a little magnetic pellet into the reaction mixture which sits atop a spinning magnet within in the hotplate. The spinning magnet causes the pellet to stir which means I don’t need to stir the reaction by hand – useful when you’re doing multiple reactions at once.

I also have a temperature probe that allows me to set a reaction at a particular temperature and keep it there. Once or twice I’ve forgotten to put the probe in my reaction mixture which causes the hotplate to continue heating up and “nuke” my reaction, which is not a good sight to come back to. Hotplates only going up to 300 °C or so.

My hood also typically contains racks of test tubes from column purifications. These racks are full of mixtures that have been separated into their components by running them through a column of silica gel – the little bags you find in new shoes and bags to absorb moisture. Much of my time is spent rinsing out these test tubes into my waste bottle when I’ve isolated the products from the test tubes I need.

My Thin Layer Chromatography (TLC) tank is where I run larger TLC analytical experiments, otherwise, I use a beaker for plates that aren’t as wide as the one pictured. You may have carried out a separation of pen inks in school using paper chromatography. TLC works by the same principle of allowing a liquid to run up a rectangular plate of silica to see how many components are in a reaction mixture, indicated by the number of spots seen on a plate after it has been run.

Finally, the manner of glass tubes in my hood is known as a Shlenk line and allows me to control the flow of nitrogen gas and vacuum into my hood. I can use the various taps to connect to my reaction mixtures and remove the air form them using the vacuum pump just to the outside of my hood, then flood them with nitrogen, and repeat a few times to make sure I’ve got rid of most of the air.

So there you have it. I hope you’ve enjoyed this tour of my fume hood and how I use everything in it. I’ve spent many hours standing at this hood during my Ph.D. and it helps to contain my spills and mini explosions to keep me safe from chemical harm.

I try to tidy my fume hood at the end of the day, cleaning up any spills, removing all unnecessary glassware as it can get pretty busy with several reactions and multiple flasks on the go at once! I give it a deep clean every so often before I go on holiday when I tend to have less stuff in it.

Picture caption: Fiona in lab coat and safety glasses working beside the fume hood

I hope that’s given you a flavour of what goes on in a fume hood. Usually, a school science classroom will have one for storing certain chemicals but in research, they’re used daily! Stay tuned for future posts about my desk and organisation system.

If you’re a chemist, what’s your fume hood like? Otherwise, what’s your main working space like? Let me know in the comments below.

 

PhD Update: 2019 Q1

This is the last year I’ll be spending in the lab before writing up my PhD next year. I thought it would be useful for me to blog where I am now and what I still need to do in terms of my research about once a quarter. Now that we’re at the end of March it’s time to review the last three months!

A selfie of me looking quite grumpy about some data I'm holding - a printout of a large table with lots of big numbers highlighted in red, orange and yellow

Third year started off with a bit of a rollercoaster. I had received some data back just before Christmas that I had been waiting about six months for. Most of the time I’ve been seeing how good my molecules are at shutting down one or two kinase enzymes. This experiment was slightly different in that it tested my six best molecules against hundreds of them – about 400 of the 518 found in the human body.

When I got the data back I thought it was bad news: the numbers were big for a lot of my kinases and I assumed that was a bad thing. I thought my molecules shut down far too many other kinases in addition to the one I wanted them too. This is typical of a kinase project because kinase enzymes are very similar in their shape.

It wasn’t the end of the world because I was still contributing something new to the field – you can’t drug my particular kinase. I started planning final experiments to make a few more compounds that would nicely round off my thesis to show I had tried all the sensible versions of my compounds as well as some potential new ideas to try and salvage my project.

Unfortunately, it took my collaborator who had organised the experiments a few weeks to get back to my e-mails for him to tell me I had my numbers mixed up! In this particular experiment, big numbers were good news! Very good news in fact! My best molecule only shut down 9/400 kinases.

Fiona looking embarrased with her hand over her mouth realising she made a mistake
Picture caption: Fiona standing in front of a redbrick wall with her hand over her mouth, realising her mistake

It was a huge relief in some ways that my project wasn’t, in fact, dead, but I was annoyed I had wasted a month taking my project in a completely different direction. What encouraged me though was the amount of stuff I had learned over the past couple of years and how I was able to come up with a few options for my project by myself.

Since then I’ve been working on some molecules that will round of ideally two chapters of my thesis, saying goodbye to two sets of compounds I’ve made that haven’t worked quite as well as the others. This has proved quite tricky as I’m trying to make a molecule no one seems to have made before – and as the weeks of failed chemistry go on, I can see why!

A gloved hand holding three sealed glass tubes containing failed reaction mixtures of black goop. Experiment numbers 165/166/167 written on the lids.
Picture caption: A gloved hand holding three sealed glass tubes containing failed reaction mixtures of black goop. Experiment numbers 165/166/167 written on the lids.

Once I get these molecules out the way I can focus on making smaller changes to my best compound to tweak it so that it only hits 1 kinase. That way when biologists use it they can be sure when things happen in the cancer cells they treat with my molecules, they can be relatively sure whatever change they see is due to shutting down that particular kinase.

I’m about to send away a set of compounds that will determine how long my chemistry route is going to be to each compound. At the moment, the best compound requires 9 individual chemical reactions to get to the final compound which is a lot of work for each compound! It’s because of a nitrogen atom present in a particular place that the chemistry is so longwinded.

I was able to make molecules that removed that nitrogen or moved it to another place in my compounds and swapped it for a carbon atom which reduced that chemical route to 3 chemicals steps! I’m hoping the version of the molecule where I’ve moved the nitrogen to a slightly different place will allow me to keep using a shorter chemical route, otherwise, it’s back to the long route I spent ages on in first year!

In the middle of March I attended a conference called Mastering Med Chem that was being held at the site of a pharmaceutical company called Eli Lilley based in Surrey, just a couple of hours up the road for me. I went to the conference last year and I was really encouraged coming across familiar faces and having a greater knowledge of the field in the talks I was listening to. To get a special discount I took a research poster with me and hovered beside it during coffee and lunch breaks just in case anyone wanted to talk about my research with me – which a few people did!

Fiona in business attire and wearing a conference lanyard standing in front of her A0-sized research poster summarising her PhD with a mixture of images and text. The poster title says "Design and Synthesis of Novel PRK2 Tools to Probe Cancer"
Picture caption: Fiona in business attire and wearing a conference lanyard standing in front of her A0-sized research poster summarising her PhD with a mixture of images and text. The poster title says “Design and SYnthesis of Novel PRK2 Tools to Probe Cancer”

Across all my channels (Twitter: @fi0n0 and Instagram: @thechemistryofaphd and on this blog) I started my #positperiodictable series where most weeks I post about an element of the periodic table to mark the 150th anniversary of Dmitri Mendeleev presenting his method for organising the elements to the world. I’ve managed to post the first 6 groups so far, 18 plus the f-block of superheavy radioactive metals to go!

I have also been trying to collect all the data for the molecules I made between October and December last year. I just have three more compounds to finish, then I can write up that bit of my thesis. I’m glad I’ve stuck with writing this part of my work up in thesis style, called the experimental section because it will save me a lot of time in the future.

So, in summary, after briefly thinking my PhD project was over, I’ve been trying to make some compounds that will round of large segments of my these I’m nearly there, and I think after the ups and downs of January, I don’t think I’ve been as motivated to be in the lab as much as I could have been but hopefully the next quarter will be better.

In terms of other things that happened this quarter, I enjoyed a short surprise holiday to Vienna with my partner, celebrated my 26th birthday, played in the Royal Albert Hall and got to do some fun science communication stuff on campus and in the London Science Museum so I’d say it’s been a pretty good few months. Just need to get on with the science I’m supposed to be doing!

Picture caption: Fiona holding a violin sitting on the stage of the Royal Albert Hall with her orchestra desk partner Ouli.
Picture caption: Fiona holding a violin sitting on the stage of the Royal Albert Hall with her orchestra desk partner Ouli.

How’s the start of 2019 been for you? Any highlights or challenges? Let me know in the comments below.

What’s on my lab bench?

Most people have a desk as a place of work. I’m lucky enough to have three workspaces as a chemist: my desk, my lab bench, and my fume hood, all for different aspects of chemistry research. Today I’m going to give you a tour around my lab bench!

labelled lab bench.png
Picture caption: Fiona’s busy lab bench with different items labeled, from the sink to the sample vials!

My lab bench is used to carry out low-risk tasks involving my chemical samples. Most of the work I do when handling and manipulating my reactions is carried out in a fume hood to reduce my exposure to them but small analytical tests and sample preparation can b carried out on a bench – unless my sample is particularly smelly which thankfully not many of my compounds are!

I share a sink with another chemist in my lab where we wash up our glassware. We’re a bit like a student flat in that neither of us like putting the glassware away in the cupboards so take stuff directly from the drying rack which can turn into a mountain of conical flasks and beakers sometimes!

While I use an electronic lab book for my final write-ups, I keep a rough note of what I’m doing for each experiment in these blue and while notebooks and transfer it to the ELN at the end of the experiment. If I had to grab one thing in the event of a fire, it would be these notebooks as everything else I do is digitally backed up!

I keep final products in these sample vials before transferring them to smaller ones for archive storage about once a quarter. I draw the chemical structure on the yellow circular labels to help me find samples quickly. I try to keep my samples in chronological order but it doesn’t always happen so you’ll often find me hovering over these boxes trying to find vial such and such.

Although the picture doesn’t show it too well, I have to boxes of glass pipettes on my side of the bench, individual disposable glass droppers. I have a rubber atomiser that I attach to them when I need to transfer small quantities of liquid between flasks etc. and then the glass pipette gets recycled. We have two lengths of pipette and I seem to get through the shorter ones a lot quicker than the longer ones.

The tip-ex isn’t actually for correcting written mistakes in my notebooks – I tend to just scribble. I actually use it to mark sample lids so I can differentiate them as my own from my colleagues when using shared equipment. Our group has to use black lids for our NMR tubes so I found it a simple way to identify my samples from the dozens than go on the NMR instrument carousel.

I use a ruler for drawing straight lines on my TLC plates and for measuring the distance between spots once I’ve run TLC experiments (see my How do I know I’ve made the right molecule post).

The small tubes in the little beaker are how we store samples long term. They’re obviously a lot smaller than the glass vials and we typically have less than 0.1 g of a sample left after using what we need for future chemistry. We also use these tubes for transporting samples because they have individual bar codes on them. These are six compounds that I’ve taken out of archive storage for my colleague in biology to come to get whenever she needs them.

The conical flask on my desk contains empty NMR tubes, long skinny glass tubes used to prepare a sample for a particular type of analysis that investigates the magnetic character of the compounds – again see my previous post for more detail. The tubes are capped with the black lids I cover in Tipex.

I don’t keep many chemicals on my desk but these two are for a public engagement activity I’m doing with schools soon and so because they weren’t bought using the group’s research budget, need to be stored separately from the other chemicals I use, which are typically stored under my fume hood or in one of our several filing cabinets.

A calculator is a chemist’s best friend for double checking sample dilution factors and scaling reactions up to bigger quantities (like doubling a recipe). My electronic lab book does a lot of calculations for me but there are always some that need to be done manually like converting concentrations units from % to molar etc.

I hold on to my NMR samples until I’ve definitely got everything I need to write-up an experiment. Cleaning these tubes out isn’t the most fun job in the world so I tend to wait until I have a lot of tubes to clean before the repetitive task of rinsing them out.

My colleague and I share a number of things on our bench like sample vials and empty plastic columns for purification. We try to keep them topped up for each other.

Every chemist needs gloves for handling chemicals. I try to not get through more than a couple of pairs of gloves a day having mastered the technique of removing them in such a way that they can be worn again if I know I’ve been particularly careful and not got much on them.

My green tray has samples ready for being archived. I got this from a colleague who was leaving and it’s the perfect size for storing out mini sample vials. Scientists are a bit like vultures when they know there’s a free for all during a lab clearout or someone moves job, we become quite territorial about our pieces of lab kit.

My cardboard box has random bits and pieces in it like pencils and stickers for my lab vials.

I also have a mountain of plastic rings for storing round-bottomed flasks – spherical pieces of glassware that as you can tell by the name don’t stand up very well on their own.

Sometimes I get deliveries in the post in boxes that I bring into the lab. This tiny box was the perfect size for storing my TLC plates.

The laminated sheets are for writing the reaction schemes for what’s going on in my hood if I’m leaving a reaction on overnight. It allows colleagues and security to check a reaction is running at the temperature it is supposed to and hasn’t randomly heated up or cooled down overnight.

Lastly comes my vacuum pump which is attached to my rotary evaporator. My rotary evaporator, or “Buchi” as they’re named after one particular brand that makes them, is a bit like a kettle.  Attach round-bottomed flasks to it and boil off liquid solvents that I’ve dispersed my reaction in. The vacuum pump allows me to boil te solvents off at much lower temperatures than usual.

You may know about the phenomenon where water boils at a lower temperature at the top of Everest due to the reduced air pressure. My Buchi takes this to the nth degree by creating a vacuum and can actually boil water off at 40 °C! The samples sit in the water bath which is warmed to my desired temperature and rotates to maximise even distribution and mixing of my reaction mixture while also creating a thin film of solvent which then evaporates more easily.

The shelf above my bench contains frequently used chemicals for reaction work-ups/purifications. It includes various acids, bases, substances for removing water, stuff for preparing columns and my NMR solvents. We also have parafilm, a bit like clingfilm, used to seal vials and chemical bottles to stop samples or reagents from going off.

I hope you’ve enjoyed my lab bench tour. Stay tuned for future posts about my desk and fume hood.

What’s your working space like? Let me know in the comment below.

#postitperiodictable Group 2

The second column elements of the periodic table are known as the alkali earth metals. They are like group 1 in that they are relatively soft metals that react with water to produce hydrogen gas however they don’t react as vigorously.

Picture caption: post-it note showing beryllium, element number 4, is used to make springs in electronics

This is due to the group 2 elements having 2 outer electrons instead of one. This is a slightly more energetically favourable electron configuration, meaning the atoms in group 2 are happier with two electrons whizzing around the nucleus than group 1 metals are with their single electron, who just want to give it away as quickly as possible to form their preferred state as a positive metal ion (M+, where M stands for a metal).

Picture caption: post-it note showing magnesium, element number 12, plays an important role in photosynthesis, the process by which plants use light energy to convert carbon dioxide and water into glucose and oxygen gas – the reverse of what our bodies do.

Group 2 metals aren’t precious about their two electrons though. They are also happy to exist as positive metal ions that have lost their negatively charged electrons, but they tend to form M2+. If they formed M+ they would then have a similar electron configuration to a group 1 element which we know isn’t very stable and would get rid of that second electron as quickly as they can.

Picture caption: post-it note showing calcium, element number 20, which makes up a significant component of our bones

This relatively lower reactivity means that group 2 elements are often used in portable hydrogen generators because they release hydrogen slowly enough that there isn’t sufficient heat energy given out over the course of the reaction to ignite the flammable hydrogen gas – which is what we see when group 1 metals react with water.

Group two metals are shiny and usually silvery-white in colour. Some occur naturally as free elements but are often found as ores (typically metal oxides) in the ground and the metal needs to be extracted from those compound mixtures.

Picture caption: post-it note showing strontium, element number 38, which is used to make fireworks appear red in colour

Much like Group 1 the reactivity of the metals increases going down the group because the outer electrons become further away from the nucleus with the increasing number of electrons moving around the nucleus, making them easier to remove – much like how a paperclip becomes easier to manipulate the further away it is from a magnet.

The metals react with water to form metal oxides but because of their 2-electron valency, they form hydroxides with the general formula M(OH)2 as hydroxide (OH) ions have a single negative charge so two are needed to balance the double positive metal ion (M2+). Beryllium is the exception which has a sufficiently protective oxide layer.

Picture caption: post-it note showing barium, element number 56, rarely used but can be found in some paints

They also react with oxygen to form metal oxides and with halogens, such as chlorine, fluorine etc., to form metal halides.

Throughout group 2 we’ve learned about beryllium’s niche role in missiles and rocket parts; the bright light burning magnesium produces which is used in old photography flashes, flares and fireworks; calcium’s key role in forming our bones and teeth and how strontium can be used to mimic calcium to treat osteoporosis; and the lesser used barium and radium which are used for treating digestive disorders and prostate cancer respectively.

Picture caption: post-it note showing radium, element number 88, which used to be used to be painted onto watches to make components glow in the dark

I hope you’ve enjoyed our tour of group 2. Now we move on to the central block of the periodic table, known as the transition elements which spans groups 3 to 10! Keep an eye on the Instagram account for individual posts about each element as well as other content about my life in the chemistry lab.

What’s your favourite element? How are you marking #IYPT2019 ? Let me know in the comments below.

 

#postitperiodictable Group 1

Every day last week I posted about each element in the first column of the periodic table to mark the International Year of the Periodic Table on my instagram account. Elements are grouped in columns based on their properties and in this post I’ll talk about how the group 1 elements are chemically similar.

Picture caption: post-it note showing hydrogen, element number 1, which is used in buses that as a green fuel source

On the extreme left of the periodic table lie the alkali metals. Alkali because when they come into contact with water they form alkaline species e.g. lithium forms lithium hydroxide.

Picture caption: post-it note showing element number 3, lithium, used in all kinds of batteries

Hydrogen is a bit of an anomaly for this group but technically belongs to group 1 because like its fellow members, it only has one outer shell electron, known as a valence electron, available to interact with other atoms.

Picture caption: post-it note showing sodium, element number 11, which is found in table salt (sodium chloride, NaCl)

This single electron is what makes these elements so reactive because atoms prefer to have full stable complements of electrons and they are eager to rid themselves of this electron, which is relatively easy to do, in order to gain a more stable electron configuration.

Picture caption: post-it note showing potassium, element number 19, which has important applications in fertilisers

Aside from hydrogen, alkali metals are soft metals that react with air and water, meaning they are rather fun to through into a lake. When they react with water they release hydrogen gas, some in more violent ways than others.

Picture caption: post-it note showing rubidium, element number 37 which makes purple fireworks

Their flammability and reactivity increase going down the table. The YouTube channel Periodic Videos have some really nice videos demonstrating these reactions.

Picture caption: post-it note showing caesium, element number 55, used in atomic clocks

Lithium is a slow burner and takes its time converting to its metal hydroxide. Sodium will fizz while potassium bursts into violet flames. Rubidium and caesium explode when they contact water while francium is too radioactive and usually explodes without needing to be hydrated.

Picture caption: post-it note showing francium, element number 87, which has few uses because of its radioactivity

Alkali metals also react with oxygen to form metal oxides, or in the case of hydrogen, forms water, one of the key molecules of life. We are made up of 55-60% water.

They also react with halogens (group 7 elements) to form salts such as sodium chloride which we enjoy on all manner of foodstuffs. Lithium powers our laptops and cars, potassium and sodium keep the electronic signals from our brain to our body in check and rubidium and caesium help keep us on time through their use in atomic clocks.

Next we shall move across the periodic table to group 2 to a similar class of elements, known as a the alkali earth metals.

What’s your favourite element? How are you marking #IYPT2019 ? Let me know in the comments below.

What do the numbers on the periodic table mean?

2019 marks the UN’s International Year of the Periodic Table or #IYPT. It’s 150 years since Dmitri Mendeleev presented his organisation of chemical elements to the world. The periodic table is used daily by chemists and other scientists as reference resource for the ingredients of the universe.

dmitri mendeleev statue dmitrimendeleev.com
Picture caption: A statue commemorating Dmitri Mendeleev surrounding by a radial presentation of his periodic table, in source: dmitrimendeleev.com

Ancient Greeks defined “elements” as one of the following four: earth, fire, water and air. They were used to explain how matter worked. Since the elucidation of atomic theory, scientists have broken the universe down into 118 chemical elements.

the four elements learner.org
Picture caption: the four classical elements and the descriptors used to classify them. Source: learner.org

Atoms can be thought of as small particles that make up everything but even they are made up of smaller components, known as sub-atomic particles, and the number of sub-atomic particles in each atoms defines what element the atom is. The three sub-atomic particles we learn about at school are protons, neutrons and electrons. Protons, neutrons and electrons are made up of even smaller components but as I am not a physicist, I’m not so concerned about looking at matter at that scale.

atomic structure explainthatstuff.com
Picture caption: the structure of an atom – a central nucleus made up of protons and neutrons surrounded by fast moving electrons. Source: explainthatstuff.com

Protons are positively charged, electrons are negatively charged and neutrons, as you might guess from its name, are neutral. The number of protons and electrons in a neutral atom are the same in order to balance the charge. An atom’s structure is made up of a central nucleus made up of protons and neutrons with electrons whizzing around the nucleus.

Because the electrons are on the exterior of the atom they are the particles that are actually involved in chemical reactions. Electrons can be completely transferred from one atom to another – in a process known as ionisation which forms ions, charged atoms – or they can be shared between two atoms to form a chemical bond. The degree of sharing between two atoms dictates what type of chemical bond has formed.

bonding weheartit.com
Picture caption: cartoon depicting the different ways atoms share valence electrons to form chemical bonds. In a covalent bond electrons are share fairly equally between atoms; in metallic bonds the electrons are not associated with specific atoms; in an ionic bond one atom loses an electron for another to gain that electron and a coordinate bond occurs when an atom donated two electrons to another atom. Source: pearlsofrawnerdism.com

Most of an atom is made up of empty space: if an atom were the size of a football stadium the nucleus would probably only take up the space of a marble sitting in the centre of the playing ground!

A standard periodic table will usually have 2 elements associated with each element: the atomic number and relative atomic mass number of that element. The atomic number can be defined as the number of protons present in the central nucleus of the element’s atom while the mass number is the total number of protons and neutrons in the nucleus. The mass number is the larger of the two numbers found associated with an element in the table.

The mass number can be quantified by a constant (a number that is shown to stay the same across numerous calculations) called Avogadro’s number. Avogadro’s number is 6.02 x 10^23. Essentially, what Avogadro’s number describes is the number of atoms you need of a particular element for the weight of your sample to match the mass number in grams.

A single unit of 6.02 x 10^23 atoms is described as a “mole”. It’s a bit like saying you have “a dozen” eggs = 12 eggs. A “mole” of atoms is 6.02 x 10^23 atoms which, if your element is carbon, would equal 12 g because 12 is the mass number of carbon.

moles hinkhousescience.com
Picture caption: a happy cartoon mole placing 6.02*10^23 carbon atoms on a scale to make 12 g of carbon (aka one mole!) credit: hinkhousescience.weebly.com

The number of neutrons does not correlate perfectly with the number of protons, its more to do with the number of neutrons required to allow that number of protons to be in close proximity with each other while maintaining stability – imagine trying to force two magnets together. They repel, much like the positively charged protons do if they get too close together.

The presence of protons in the nucleus makes the nucleus overall positively charged and the electrons whizz around within the proximity of the nucleus because they, as negatively charged particles, are attracted to that positively charged nucleus.

As an element gets bigger – with more and more protons, neutrons and electrons packed into its structure – its properties change. The smaller elements at the top of the periodic table are gases like hydrogen (atomic number 1), helium (atomic number 2) and oxygen (atomic number 6) while the heavier elements towards the bottom of the table are metals like gold (atomic number 79), lead (atomic umber 82) and uranium (atomic number 92).

phases pt periodictable.com
Picture caption: periodic table coloured according to the phase (solid, liquid, gas) an element exists in at room temperature. Most elements are solid, coloured red; some gas (blue) and only two are liquid, bromine and mercury. Source: periodictable.com

Mendeleev chose to arrange the elements by atomic number rather than mass number and very cleverly left gaps because at the time there were only 56 known elements. He was successfully able to predict the properties of the yet undiscovered elements, such as germanium, gallium and scandium.

There are other periodic tables that have additional information on them such as the size of atoms, density of elements and melting points. Trends can be seen as you go along the rows and columns of the periodic table, which I may discuss in further detail in a future post. But normally the most basic ones have the atomic and mass numbers of each element on them, as well as the symbol used to abbreviate the element’s name.

desnity pt periodictabloe.com
Picture caption: Graphic showing the increasing density of the elements going down the periodic table and also peaking in the middle of the table going left to right. Source: periodictable.com

On my Instagram and twitter account I will be posting about each element over the course of this year and will summarise each column of the periodic table in a longer blog post here. I hope you enjoy exploring the periodic table with me this year along with everyone else marking #IYPT as we learn about the stuff that makes us and everything around us.

Did you learn about the periodic table at school? Do you have a favourite element? Let me know in the comments below.

 

Science Conferences I went to in 2018

Over the course of a PhD, students are encouraged to leave the lab from time to time to go to conferences to learn about other kinds of research going on in their field. Science conferences gather researchers from academia and industry. In this post I will talk about the different conferences I went to in the second year of my PhD in 2018 and what I learned from them.

January – Genome Stability Network Meeting, Cambridge

The Genome Stability Network is a group of scientists interested in learning about how the DNA in our cells is damaged and repaired, usually with the aim of utilising these processes to treat cancer. At the start of 2018 I attended the annual meeting of the GSN and heard a lot of talks about different aspects of DNA damage and repair processes.

While I’m pretty sure I was the only chemist in the room – a lot of this work is carried out by biologists establishing the pathways by which these processes take place in cells – it was useful to see what themes emerged across the few talks.

March – Mastering Medicinal Chemistry, Glasgow

Picture caption: A metal sign at the bottom of some stairs pointing the way to the Mastering MedChem conference
Picture caption: A metal sign at the bottom of some stairs pointing the way to the Mastering MedChem conference

I had the opportunity to go back to my old university, University of Strathclyde, where I completed my undergraduate MChem degree for a medicinal chemistry conference aimed at early-career researchers. The talks covered a whole range of disease areas and approaches and I also took a poster summarising my own research to talk to people about during the coffee breaks.

I learned about new unconventional ways of finding starting point molecules (“hits”) to start new drug discovery projects, as well as hear from someone from pharmaceutical company AstraZeneca about a project similar to my own. It was useful to exchange ideas with the speaker to help my own project.

There was also a panel where the speakers were asked about their outlook on the future of the drug discovery industry, which I sadly learned was sounding bleak on all fronts. RxNet asked me to write a more detailed conference report which can be found here.

May – Kinase 2018, Cambridge

Picture caption: Fiona giving a presentation to a group of scientists in front of a slide titled "Designing PRK2 tools to treat cancer". The slide has pictures of enzymes and chemical structures, giving a snapshot of my PhD project
Picture caption: Fiona giving a presentation to a group of scientists in front of a slide titled “Designing PRK2 tools to treat cancer”. The slide has pictures of enzymes and chemical structures, giving a snapshot of my PhD project

The first two conferences were relatively general in their subject matter. In May I returned to chemistry for a much more focused meeting around kinases.

Kinases are signalling proteins (enzymes that tell a cell to do something) and are implicated in many diseases, particularly cancer. There are 516 kinases in humans so there are lots of opportunities to target them in different ways to treat patients.

I learned a lot about the different disease areas kinases are being targeted for as well as what the trendy kinases were that a lot of researchers seem to be looking at just now.

At this conference I got the opportunity to give a 2 minute, single-slide “flash presentation” about the poster I had brought. While having such a small amount of time to sell my research was challenging, I noticed a huge difference between the number of people who came over to my poster to chat to me afterwards.

If you’re attending a conference and are nervous about applying for such a slot I highly recommend it, it’s over in a flash and resulted in many more useful conversations about my work than if I hadn’t done it.

December – Chemical Probes in Systems Biology, London

Picture caption: the entrance to a stately building, Burlington House in London, with "Royal Soc of Chemistry" in gold above the door. There is a Christmas tree and an old lamp post next to the door.
Picture caption: the entrance to a stately building, Burlington House in London, with “Royal Soc of Chemistry” in gold above the door. There is a Christmas tree and an old lamp post next to the door.

At the end of the year I popped up to the Royal Society of Chemistry’s headquarters at Burlington House to attend the smallest of the conferences I have been to. There were roughly 50 people present and was very relevant to my project – the title conference alone would work as a thesis title for my project.

I’ve found it encouraging to note over the course of the last couple of years I’ve become familiar with “names” and institutions in my field. The first talk was by someone from the institute I collaborate with on my project and another speaker was someone I had previously applied to do a PhD with.

I had applied to speak at this conference but my application was unsuccessful. I was still able to take a poster and the collaborator I mentioned gave me some useful insight about some data I had been waiting a while for regarding my project.

Hopefully I will get to speak about my PhD at a conference in my third year – and it would be especially nice to get to travel abroad to a conference.

Have you been able to travel anywhere exotic for conferences in your line of work? Were they useful to attend? Have you ever given a flash presentation before? Let me know in the comments below.

Christmas may feel like its over but I have one more day of my #12DaysOfChemistmas that I’ve been sharing on twitter and instagram.

This Molecule Spells “Happy Christmas”!

It’s Christmas Eve! I hope you’re all getting to enjoy the festivities in some way, whether you’re taking a break from research/work with family and friends or taking advantage of it being quiet to get work done – or a special shout out if you’re one of the superheroes that keep the emergency services running over the Christmas/New Year period.

In true chemistry-geek fashion, I’d like to wish you a very Happy Christmas with this molecule!

MERRYCHRISTMASunlabelled
A Christmassy peptide

It might not look like it says much at first but let me explain the structure in a bit more detail. This is a peptide, that is a long chain molecule made up of individual amino acid components. The amino acid “links” are connected by amide bonds.

amide bond formation
An amide bond forms between an amino (NH2) and a carboxylic acid (COOH)

Amino acids are used to build hundreds of thousands of proteins that carry out many jobs in our bodies. There are 20 common amino acids which are typically found in biology and 9 of those are “essential amino acids”, meaning they can only be obtained by our diet and not synthesised by our own bodies.

The 20 amino acids can be categorised by their chemical structure. While all possess an amine (NH2) and a carboxylic acid group (COOH), hence the name “amino acid”, they contain side chains that branch off a central atom between the amine and acid groups.

These side chains can be categorised as to whether they contain a greasy aliphatic group of atoms or something containing an alcohol, sulfur, acidic or basic group. Andy Brunning’s infographic summarises this really nicely.

20 Common Amino Acids Physiological [EDIT].png
Amino Acid summary produced by Andy Brunning of Compound Interest
Because peptides are lengthy sequences of amino acids, its easier to abbreviate the individual amino acid chains with individual letters to succinctly describe the amino acids present within a protein:

H – histidine, a basic amino acid containing an imidazole heterocycle (ring of atoms that isn’t just made up of carbons and hydrogens)

A – alanine, one of the simpler aliphatic amino acids with just a methyl side chain

P – proline, the only amino acid that incorporates the amino acid motif into the side chain.

P – another proline

Y – tyrosine, an aromatic amino acid (contains a hexagonal benzene ring) with an alcoholic phenol OH attached.

C – cysteine, the other sulfur-containing amino acid

H – histidine, another basic amino acid

R – another arginine

I – isoleucine. Leucine is a straight chain of three carbons. Isoleucine is an “isomer” of leucine, meaning those atoms are arranged slightly differently

S – serine, an alcoholic amino group

T – threonine, the third of the three alcohol containing amino acids (serine, threonine and tyrosine). It has a slightly longer carbon chain than serine. The kinase proteins I’m trying to target in my PhD reacts with these kinds of residues in our cells.

M – another methionine

A – another alanine

S – a final alcoholic serine caps the end of our festive molecule

With that, I’d like to thank you all for following my scientific escapades so far and wish you all a Christmas period full of peace and joy and all the best for 2019.

MERRYCHRISTMASLabelled
My labelled festive peptide wishing you a HAPPY CHRISTMAS

How are you celebrating Christmas? Do you have any fun abbreviations in your work? Let me know in the comments below.

Reflections on second year

shallow focus photography of yellow star lanterns
Photo by 嘉淇 徐 on Pexels.com

This is my last week in the lab of 2018. It’s only really four days because we’re having our group’s Christmas party on Friday (laser quest and pub lunch) and then I’m at a conference on Monday before taking the rest of the week off before Christmas.

Towards the end of first year I wrote this post about how I thought first year had gone and I listed 5 things I wanted to change. In this post I’m going to see how I did with those goals and create 5 new goals for third year.

  1. Read more papers – I managed this one quite well. In first year I sporadically printed and read papers but this year I got organised and set up an RSS feed and have been pretty good at checking in with it most days – perhaps a little too often with my “inbox zero” tendencies. I use Mendeley to save anything I come across that might be useful for my project. I tried #365papers  and failed miserably though, partly due to me losing the spreadsheet I was keeping track of papers on in an IT nightmare but also me just not getting into a habit.
  2. Make more compounds – I certainly achieved this one. First year involved trying a lot of new chemistry and at the start of this year I optimised a lot of that chemistry making it far easier to get final compounds out. For example, one set of molecules I made last year took 8-9 separate reactions to get there and now with a small change to the chemical structure that I’ve learned doesn’t kill the activity of the drug in most cases, I can get to those compounds in 2-3 steps.
  3. Be more selective in the seminars I attend – In first year I felt I had to go to every single seminar to widen my knowledge but as you specialise you learn what interests you and what a good use of your time is. I still go to the odd seminar outside of my research area so I’m not in too much of a rabbit hole, but I certainly feel like I’ve been using my time a bit better when it comes to seminars.
  4. Attend more conferences – having only been to one conference in first year, I went to a few in 2018 – and still have one to go next week! I started the year by attending the Genome Stability Network Meeting in Cambridge in January, in March I went to the RSC-BMCS Mastering MedChem conference at University of Strathclyde in Glasgow, then RSC/SCI Kinase 2018 in May, again in Cambridge, and still have the RSC Biotechnology Group Chemical Tools in Systems Biology in London a week today.
  5. Use this blog more – this one I’ve technically achieved in the last month or so. Most of the year I found myself “procrasti-blogging” sporadically blogging if I was taking part in a science writing course where an assignment involved writing a blog or the Google Doodle of the day was linked to chemistry. Now I’m making a concerted effort to post regularly on here and also on my dedicated Instagram account.

I think I’ve done quite well in meeting all of those goals. They were fairly realistic goals without quantification. Now here are my goals for third year:

  1. Keep using this blog – weekly blog posts, a couple of Instagram stories/posts a week. Over Christmas I’m going to make a longer term plan for content and schedule as many posts as I can so it doesn’t take up too much of my time during term time. Let me know if there’s anything in particular you’d like to see.
  2. Get the desk/bench balance right – I continue to struggle with staying at my desk more often than being in the lab. Often I choose reading, agonising over lab book/write-up and writing off lab tasks to “tomorrow” that could be done today rather than making stuff in the lab. If anyone has any tips about this please let me know in the comments.
  3. Get something published – I have something to show for my research and I really want to get some of it published in a medicinal journal to show alongside my thesis at the end of the PhD. I’m waiting for some long-promised data from a collaborator which will help supplement my work but I’ve agreed with my supervisor that in February I need to start writing papers for publication without that research.
  4. Speak at a conference – similar to above, I have a sufficient story to tell that I would love to give a talk about just once about my research at a conference rather than just standing beside a research poster at said conferences where people may or may not come over to hear about it. I’d also like to go to a conference outside of the UK because travel is one of the perks of being in research.
  5. Finish the practical side of the project well – I plan to spend another year in the lab before writing up. I have until March 2020 technically but I’m leaving those three months as a “backstop” of sorts – #relevant. I have in my head I’d like to get to 100 final compounds for my thesis (I’m about two thirds of the way there so it seems tangible) and I’d also like to spend some time in the biology labs my group have testing some of those compounds.

Hopefully this time next year I’ll be writing a similar post about how well I did in achieving my third year goals. It’s crazy it’s got to my last year in lab already!

Did you make any goals/resolutions for 2018? Did you achieve them? If not, are you going to reattempt them in 2019? Let me know in the comments below.