To Be A Natural

Do you read labels on your box of Fruit Loops cereal or bag of Skittles candy? According to the Natural Marketing Institute, about 66% of us read food labels and look for information regarding GMOs (genetically modified organisms), preservatives, and artificial colors and flavors. Even a chocolate and peanut-flavored Pop Tart will contain ingredients that can stymie a reasonably knowledgeable consumer:

(Image from Pop Tarts nutrition information page)

TBHQ - we get a sense this is a preservative but what do the letters stand for? How does it act as a preservative?
Glycerin - ?
Modified corn starch - how was it modified?
Alkali - ?
Sodium acid pyrophosphate - ?
Monocalcium phosphate - ?
Artificial flavor - what specifically is it?
Potassium sorbate - same second question as TBHQ
Yellow 5 Lake - ?
Red 40 Lake - ?
Blue 1 Lake -?
Red 40 - ?

This is just a sampling encouraging us to wonder about the what, why, and  where did these come from. If we take a chocolate peanut butter flavored Pop Tart out of its wrapper and look at it,

(image from Dishblogger)

it looks mostly brown or tan in color, so why do we need Yellow 5, Red 40, and Blue 1? It's more obvious in these examples:

(image from Texas Monkey)

(image from Rainbow Jello Cubes)

Because of the perceived ubiquity of synthesized compounds in our food, companies are addressing public concerns about artificial colors which is what today's post will focus on. While they enhance a food product's attractiveness, we wonder about the long-term effects of consuming them and if there is potential risk of developing hyperactivity or even cancer.

The most commonly used food colors in the  United States include:

*Blue No. 1, Brilliant Blue FCF (the FCF is "For Coloring Food")

*Red No. 40, Allura Red AC

*Yellow No. 5, Tartrazine

*Yellow No. 6, Sunset Yellow FCF (this is used for making the color orange)

In Europe there has been a greater degree of substituting found-in-nature compounds for man-made, petroleum-based molecules:

Phycocyanobilin is a chromophore (a molecule that imparts color) found in cyanobacteria like Spirulina and blue-green algae. It is currently used in Europe as a substitute for Blue No. 1. 

(image 2 from Global Natural Energy; image 3 from John Kuglin/AP File Photo)

Naturex is a French company using spirulina extract to make blue colors for  candy coatings.

(image from Foodnavigator.com)

The red in red velvet cake as well as in strawberry yogurt comes from a compound known as carmine and has a natural source. A great video by Bob Alderink from the North Carolina Museum of Natural Sciences explains it here.  

(image 1 from https://commons.wikimedia.org/wiki/File:Carmine.PNG; image 2 from zoomyummy.com)

(image 1 by Jü (Own work) [CCO], via Wikimedia Commons; image 2 by Simon A. Eugster (own work) [CCO], via Wikimedia Commons)

Curcumin is a compound that comes from an Indian plant called turmeric, a relative of ginger. Besides its use as a natural alternative to yellow food dye, recent research indicates it has the ability to bind to amyloid proteins and is being considered a potential therapy for Alzheimer's disease.

Check out the labels on your packaged foods and find other natural colors from beet juice, annatto, red cabbage juice, and even purple carrot juice. A quick online search will result in many videos and recipes showing how to make natural food coloring agents. A good example from Dulce Delight shows the pH dependence of red cabbage juice as a universal indicator and as a way to make the color blue.

(image from How to Make Natural Food Coloring - Concentrated Color Recipe)

An Early Cure for Malaria as Well as a Popular Ingredient with Gin

(image from NotFromUtrecht (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0) via Wikimedia Commons

Would you believe that this popular beverage, the gin and tonic, contains an ingredient that was considered the cure for malaria during the American Civil War, World Wars I and II? Even in medical kits used during the Vietnam War, the chemical compound quinine was found among bandages and needles.

Medical tin of quinine sulfate used by surgeons during the Civil War.

(image from http://www.angelfire.com/oh3/civilwarantiques/1304webcat.html)

Here, a sargeant from Slate Hill, NY treats a malaria-strickened soldier with quinine during World War 2.

 (image from http://www.crazywebsite.com/Free-Galleries-01/USA_Patriotic/pg-WWII_Posters_Vintage/Vintage_WWII_Patriotic_Posters_United_States_America-_Malaria_1_jpg.htm)

During the Vietnam War, a chloroquine-resistant strain of malaria necessitated the use of quinine in conjunction with pyrimethamine to significantly reduce the rate of recrudescence (recurrence of symptoms after a period of quiet). Source: U.S. Army Medical Department, Office of Medical History 

Quinine is the active compound in the bark of the cinchona or "fever" tree discovered by South American Quechua Indians. When Jesuit missionaries started using it in the 17th century, it was called "Jesuits' Powder." In the 1930's, the Dutch controlled a monopoly on cinchona and provided about 20 million pounds of bark per year with quinine content as high as 13%.

 Cinchona

 (left image is Cinchona pubescens; right image is Cinchona trees from the Congo - from The Alcohol Professor)

 Because of the difficulty in growing cinchona in other places and dwindling supply, efforts were made to elucidate the structure and eventually synthesize the compound for pharmaceutical use. A German chemist named Paul Rabe provided initial evidence of quinine's structure:

 Quinine

The blue highlighted part of quinine is known as quinoline, an aromatic heterocycle that has synthetic applications for dyes, pesticides, and antibiotics.

The complete synthesis of quinine was achieved with stereochemical control by Gilbert Storck et al. from Columbia University in 2001. 

(image From Pharmacy to the Pub - A Bark Conquers the World)

This gives you an  idea of the complexity involved in trying to synthesize a natural product. The key step involves changing a ketone functional group to an imine (respectively highlighted in red):

OTBDPS stands for tert-butyldiphenylsilyl ether 

 The other cool thing about quinine is that it fluoresces when you shine black light on it!

Tonic water contains no more than 83 ppm of quinine or 83 mg/L (image and data from wikipedia). To dilute the bitter taste of quinine, a lot of sugar is added to tonic water, and some add a twist of lime.

Resources

*"The First Stereoselective Total Synthesis of Quinine"; G. Storck, D. Niu, A. Fujimoto, E. R. Koft, J. M. Balkovec, J. R. Tata, and G. R. Dake; J. Am. Chem. Soc., 2001, 123, 3239-3242. doi: 10.1021/ja004325r
*From Pharmacy to the Pub-A Bark Conquers the World: Part3
*Jesuits' Powder
*Products of the Empire: Cinchona A Short History

Saving Sight Using Geometrical Isomerization and Channel Rhodopsin

Professor Sheila Nirenberg of Weill Medical College in Cornell University has been breaking new ground in the field of merging neural coding with mathematical equations in order to develop a prosthetic device that improves by leaps and bounds the severely impaired vision of people who have been diagnosed with retinitis pigmentosa or macular degeneration.

"Fundus of patient with retinitis pigmentosa, mid stage" by Christian Hamel - Retinitis pigmentosa by Christian Hamel. Licensed under CC BY 2.0 via Wikimedia Commons

Retinitis pigmentosa is an inherited condition that appears as darker pigmentation found in the epithelium of the retina, causing tunnel vision initially and eventually leading to blindness. The degeneration of light-sensitive photo-receptor cells is irreversible in both retinitis pigmentosa and macular degeneration.

The remarkable research that Dr. Nirenberg and her colleague Dr. Chethan Pandarinath (an electrical engineer now at the Neural Prosthetics Laboratory at Stanford University) have done is to view the process of vision this way:

 (Image from TEDMED talk by Dr. Nirenberg; http://www.ted.com/talks/sheila_nirenberg_a_prosthetic_eye_to_treat_blindness?language=en#t-135375)

The highlighted front end cells or photoreceptors of the retina respond to the image that we see in the form of a code. Then the output cells (orange balls) interpret the code and create numerous signals or action potentials that eventually travel to the brain which processes them into the image we see.

In a degenerative eye disease like retinitis pigmentosa, the front end cells are lost. So no visual encoding occurs. The solution proposed by Nirenberg and Pandarinath is to create a microchip that can mathematically encode the image ("encoder"):

(Image from TEDMED talk by Dr. Nirenberg; http://www.ted.com/talks/sheila_nirenberg_a_prosthetic_eye_to_treat_blindness?language=en#t-135375)

The transducer is a light-sensitive protein that fires the action potential signals. Currently, there is no prosthetic device superior to the visual enablement of this technology, and Dr. Nirenberg has plans to submit her research by the end of this year to the FDA for approval. If all goes well, a small clinical trial will begin in early 2016, implementing a prosthetic device (glasses) that requires little invasive surgery:

(Image from TEDMED talk by Dr. Nirenberg; http://www.ted.com/talks/sheila_nirenberg_a_prosthetic_eye_to_treat_blindness?language=en#t-135375)

  
Here, the glasses contain the microchip encoder that will mathematically interpret the images and send the code to the light-sensitive transducer cells or channel rhodopsin.

The transducer is known as channel rhodopsin, a protein that can form a channel when activated by light:

 (Image from https://justinpamute.files.wordpress.com/2010/06/rhodopsin1.gif)

Rhodopsin itself is composed of 2 components: opsin and retinal. Let's take a look at this latter molecule which has some interesting structural characteristics.

I highlighted the purple double bond to point out that retinal exhibits geometrical isomerism, a feature many alkene molecules have where they show differences in spatial arrangement around a carbon-carbon double bond. Upon exposure to visible light (the part of the electromagnetic spectrum we can see), the molecule changes from the trans to cis isomer. This reaction is important in the function of channel rhodopsin as it allows the protein to create a larger opening (by ~6 angstroms) and enables ions to travel through the channel and generate an action potential.

(Image from http://www.biophys.mpg.de/de/bamberg.html)

The YFP stands for yellow fluorescent protein which is found in green algae.

Fortunately for people with macular degeneration or retinitis pigmentosa, vision remains a possibility as long as trans- to cis-retinal isomerization can occur in this light-activated channel opening of rhodopsin.

For this innovative work, Dr. Nirenberg was awarded the MacArthur "Genius" Award. 

Resources

*Nirenberg Lab, Department of Physiology and Biophysics, Weill Medical College of Cornell University
*Retinal prosthetic strategy with the capacity to restore normal vision; S. Nirenberg and C. Pandarinath; Proceedings of the National Academy of Sciences (PNAS); vol. 109, no. 37, pp 15012-15017.
*"A Prosthetic Eye to Treat Blindness" (TEDMED 2011 talk by Dr. Nirenberg; October 2011)
*MacArthur Fellows/Meet the Class of 2013/Sheila Nirenberg
*Method of the Year 2010: Optogenetics - by Nature

Department of Physiology and Biophysics and a member of the Institute for Computational Biomedicine at Weill Medical College of Cornell University - See more at: http://www.macfound.org/fellows/899/#sthash.fXVHrHd7.dpuf

Astressin B: The Accidentally Discovered Cure for Stress-Induced Baldness in Mice

In researching compounds that may alleviate the effects of Cushing's Syndrome (symptoms from prolonged exposure to the stress hormone cortisol), the team of L. Wang, M. Million et al. made a significant discovery in using synthesized astressin-B on balding young mice that were genetically engineered to produce more cortisol. Baldness or alopecia has been linked to extreme stress, and the biochemical pathway involves several compounds.

(image from http://journal.frontiersin.org/article/10.3389/fneur.2013.00021/full)

When we perceive stress, the hypothalamus in our brain produces corticotropin-releasing hormone (CRH) which signals the nearby anterior pituitary gland to secrete adrenocorticotropic hormone (ACTH). This travels through the bloodstream to the adrenal cortex (the outside part of the adrenal gland that sits above the kidneys) and stimulates it to produce cortisol, a steroid molecule:

  Cortisol (By Calvero. [Public domain], via Wikimedia Commons

Steroids are easily identified by this 4-ring system - three of them have 6 carbons, and one has 5 carbons.

 Since CRH is the chemical key that starts this process, we should take a look at the complexity of its structure which has been designed by evolution:

 (image from chemBlink, http://www.chemblink.com/products/86784-80-7.htm)

A rather long strand of 41 peptides

So how does astressin B work in all of this and help prevent baldness in mice? The above mentioned authors (from the David Geffen School of Medicine and the Salk Institute for Biological Studies, respectively) collaborated with their team to see how this molecule can act as an agonist to CRH and thereby alleviate the symptoms of elevated stress in mice genetically engineered to overexpress CRH. What they discovered was a noticeable increase in hair growth after only 5 days of treatment with astressin B (5 micrograms intraperitoneal injection/day/mouse).

 

(image from http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0016377)

Row A mice were injected with a saline solution; row B mice were injected with astressin B and are shown 3 days later; row C mice are the same mice from row B, 4 weeks later)

So what does astressin look like? As you can imagine, it is similar to CRH in that it is also a rather long polypeptide:

Resources:

*Wang L, Million M, Rivier J, Rivier C, Craft N, et al. (2011) CRF Receptor Antagonist Astressin-B Reverses and Prevents Alopecia in CRF Over-ExpressingMice. PLoS ONE 6(2): e16377. doi:10.1371/journal.pone.0016377

 

Survival of the Fittest! Chemistry Boot Camp at MIT

Have you been stressed by your chemistry lab experience? You're not alone - every January, groups of freshmen at MIT take a class called 5.301 Chemistry Lab Techniques, also known as "Chemistry Boot Camp". Noted for its intensity and very short period (4 weeks), students learn techniques and equipment that are commonly used in a chemistry research lab - NMR, organic synthesis, crystallization, gravity filtration, rotovap, thin-layer and column chromatography. In the process of learning, they spill chemicals, break glassware, generate toxic gases, and share some of their anxieties of meeting the challenges this course entails. During the course, each student has a transformative moment that helps them decide if they are meant for research.

The videos document the journey of these freshmen from nervous newbie to savvy lab assistant, all of whom survive the ordeal and emerge with newfound love for research and chemistry.

Being in chemistry lab is a human experience. There is laughter, crying, and cursing. But in the end, there is bonding and friendship from sharing a sometimes difficult experience together.

Episodes of Chemistry Boot Camp at MIT

Same or Different? How a Simple Carbon Atom Leads to Complex Natural Compounds

A deceptively simple atom like carbon exhibits diverse styles of bonding that can lead to a plethora of complex organic molecules:

Carbon's flexibility in bonding makes it possible for molecules to have structural complexity, such as nonsuperimposable mirror images known as enantiomers:

In this example, these are not the same molecule even though the way the individual atoms are connected is the same. Because the 3-dimensional spatial arrangement around the central carbon atom is different, these are also known as chiral molecules or enantiomers, and carbon is called a chiral center.

There is a nice video created by Lydia Flynn where she demonstrates how molecules can be chiral using molecular models.

Chirality/Basic Concept Explained

Chiral molecules can be found in nature, and sometimes we need an extra few seconds to check if we are seeing the same molecule or two different molecules. One example is a compound produced female gypsy moths known as disparlure. It turns out that only one form of this molecule (in purple) is attractive to male moths.

 

Female Gypsy Moth

"Lymantria dispar 8-8-2006 19-20-14" by Opuntia. 

Licensed under CC BY-SA 3.0 via Wikimedia Commons

Molecular models show these are enantiomers and not the same molecule of disparlure.

Brown tube sponge from the National Museum of Natural History (image by Rachel Cooper)

Sceptrin is a compound made by the brown tube sponge. It is currently researched for its antibiotic potential.

 

These are enantiomers of sceptrin, a compound whose structure was first synthesized in 2004 by scientists in The Scripps Research Institute.

Molecular models again illustrate the nonsuperimposability of these mirror image isomers.

The Most Astounding Fact-by Neil deGrasse Tyson

He was asked by a Time reader, "What is the most astounding fact you can share about the universe?" This beautifully edited video by Max Schlickenmeyer highlights Dr. Tyson's answer. Essentially the chemistry that created the atoms and elements of the universe is the same chemistry made us. That is how we are connected to the universe.

His eloquent response is here.

Image credit: NASA/CXC/SAO: X-ray; NASA/JPL-Caltech: Infrared