94 Elements-Stories from Hydrogen to Plutonium

This is well worth the time viewing if you are interested in the periodic table of elements and the human element.

94 Elements

In the tab labeled "Mix Lab", there are several compounds and an invitation for the viewer to figure out the elements that make up that compound. Once you determine the correct elements and their placement, the molecular formula unlocks another short film revealing its connection to humanity.

My recommendation is sodium thiopental.

The Mix Lab

Enjoy!

Feeling Sick from Cancer Treatment? Taking Some Ginseng May Help

(image from https://www.youtube.com/watch?v=2yOuzjdzBZE)

The distinctive resemblance to a human form has encouraged Chinese to call this plant a "man root", as illustrated by the characters.

These strange-looking roots are from a plant called Panax ginseng C. A. Meyer, also known as Korean or red ginseng. The roots shown above are fresh, but when steamed and dried for preservation, they appear more dark brown-red in color.

(image from herbshow.en.alibaba.com)
The word Panax comes from Greek, meaning "all heal". Panax ginseng C. A. Meyer is commonly cultivated in Korea, Japan, China, Russia, and Germany. This species is different from American ginseng or Panax quinquefolius which is found in North America.

Since the beginnings of herbal medicine about 5500 years ago in China, ginseng has been believed to promote overall well-being, improve immunity, extend longevity, lower blood pressure, lower blood sugar, reduce nausea from cancer treatment, alleviate stress, and act as a type of "natural Viagra". Compounds called ginsenosides have been studied for their contribution to these effects, and now there is another type of molecule reported in the Proceedings of the National Academy of Sciences for its ability to alleviate nausea from anti-cancer radiation therapy. 

By Physchim62 (Own work) [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons

Ginsenosides are made of a steroid (4 connected rings), connected sugar molecules (6-membered rings), and a double bond.

In research conducted by Samuel Danishefsky et al. from Memorial Sloan-Kettering Cancer Center and Columbia University, derivatives of panaxytriol (a molecule that has two acetylene and multiple alcohol functional groups) have shown to help decrease some of the deleterious effects of cancer radiation therapy among tested mice: nausea, weight loss, the destruction of red and white blood cells (hematotoxicity), and weakness in the outer limbs due to nerve damage (peripheral neuropathy).

Panaxytriol is found at higher concentrations in red ginseng. Its derivatives are studied for their effectiveness in killing cancer cells and providing some relief at subtherapeutic doses when taken with anti-cancer agents like Taxol and 5-flurouracil (5-FU) which can have toxic side effects.

(image from https://discoveringdairyland.wordpress.com/)

Ginseng likes to grow in shade and takes at least 4 years to grow before harvest.

 Rather than extracting panaxytriol from Korean ginseng (which can be expensive given that the roots can be as high as $1400 per pound), the compound was synthesized by using an organic reaction called a Cadiot-Chodkiewicz coupling. Here is a general form of the reaction:

Through an oxidative addition/reductive elimination and use of a copper catalyst, you can connect two acetylene functional groups a bond away from each other. Panaxytriol was successfully synthesized this way in 42% yield.

An early finding by S. J. Danishefsky's team highlighted improved activity against cancer cells when the diol was changed into an acetonide.

 

The acetonide (a combination of acetone and a diol) is known to be a good protecting group of 1,2-diols and can be removed with water and dilute acid. 

 How are acetonides made? With a little acetone and dilute acid, a 1,2-diol gains protection from a protonated acetone molecule.

 For more information:

*Multifaceted cytoprotection by synthetic polyacetylenes inspired by the ginseng-derived natural product, panaxytriol; T. C. Chou; H. Dong; X. Zhang; X. Lei; J. Hartung; Y. Zhang; J. H. Lee; R. M. Wilson; and S. J. Danishefsky; DOI: 10.1073/pnas.1111332108

*Brief Introduction of Panax ginseng C. A. Meyer; T. K. Yun; http://www.ncbi.nlm.nih.gov/pubmed/11748372
 

How Brain Chemistry Deals with Chronic Stress - An Enzyme Called PTPB1

image from http://www.keepcalm-o-matic.co.uk/p/keep-calm-and-breathe-deeply-36/

Chronic stress is debilitating, and conventional treatments have involved prescribing benzodiazepines like Xanax and Valium.

Images from http://www.webmd.com/drugs/2/drug-9824/xanax-oral/details#images and

http://www.webmd.com/drugs/2/drug-11116/valium-oral/details#images

 Benzodiazepines are basically fused rings of benzene and diazepine.

Over long term use, benzodiazepines can become problematic by affecting a person's memory and attention span. Plus, their non-specificity in treating that part of the brain causing anxiety makes us wonder if we should look into the chemistry behind it. 

Now a team of scientists led by Hsiao-Huei Chen at Ottawa Hospital Research Institute has looked into the neurochemistry of stress in mice and focused on several key players in an elaborate cycle that involves endocannabinoids, hydrophobic molecules that act as signalling compounds to alleviate anxiety.

Anandamide or N-arachidonylethanolamine (AEA). The word ananda comes from the Sanskrit meaning "joy or bliss". Endocannabinoids are produced in the body and interact with the same brain receptors as THC or tetrahydrocannabinol, the active ingredient in marijuana.

As we delve into the neurochemistry of stress, we see there are two principle areas involved: the hypothalamus and the amygdala.

image from learn.genetics.utah.edu/content/epigenetics/rats/

The amygdala is important in the processing of memory, making decisions, and interpreting information from your senses into emotions (most notably fear).

The hypothalamus is important in secreting hormones that control body temperature, hunger, thirst, fatigue, sleep, and circadian rhythms.

The chemistry of anxiety is pretty complicated and is simply presented with its key players, based on the research of Dr. Chen's team:

When a mouse is exposed to 30 minutes of stress-producing confinement, a steroid called corticosterone is produced in the adrenal cortex above the kidneys.

image by Bryan Derksen (Own work using: BKchem) [Public domain], via Wikimedia Commons

Corticosterone is involved in the regulation of energy, immune reactions, and stress. In people, it is an intermediate in making aldosterone which is a major moderator of sodium and potassium ions. 

This affects a protein called LMO4 which stands for "LIM domain only 4". A LIM domain is basically a structural framework composed of two zinc ions coordinated to two amino acids, and each zinc is connected to a protein strand.

image by Bassophile at CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons

In this example of a LIM domain, zinc ions are gray; beta sheets are yellow; an alpha helix is red; and the protein strands are green.

While zinc stabilizes the protein folding, the 2-amino-acid connector provides a hydrophobic core to the structural domain, and the protein strands at both ends are different enough to provide many places for binding different molecules. 

How does corticosterone affect LMO4? Experiments reveal that increasing corticosterone causes a decrease in palmitoylation of LMO4. This is an organic reaction of attaching palmitic acid to cysteine residues of a protein. Doing this increases the hydrophobic nature of a cell's membrane. 

CoA represents coenzyme-A. The reaction is reversible because the product contains a thioester, essentially like an ester but with a sulfur instead of an oxygen atom.

Preventing this reaction causes LMO4 to remain inside the nuclei of nerve cells, and this hinders LMO4 from interacting with another important player: PTP1B which stands for protein tyrosine phosphatase and is an enzyme in the hypothalamus.

image of PTP1B by Emw (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0), via Wikimedia Commons

This enzyme has been studied for its potential in treating obesity and type 2 diabetes but its ability to dephosphorylate tyrosine and cysteine residues may also be important in the anxiety cycle.

PTP1B does the dephosphorylation in 2 steps, and hydrogen bonding helps orient the water molecule long enough to remove the phosphate group from a cysteine residue.

Mechanism from NK Tonks, http://www.ncbi.nlm.nih.gov/pubmed/12829250

In allowing PTP1B to increase in the hypothalamus and enhance dephosphorylation, a metabotropic glutamate receptor called mGluR5 is less able to participate in signalling that would lead to the production of endocannabinoids. 

As a metabotropic receptor, mGluR5 indirectly affects ion channels in the post-synaptic neurons in the brain.

The result is that the mice appear more anxious.

Photo credit: Kuttelvaserova Stuchelova, via Shutterstock

The suggestion proposed by the research team is to control the activity of PTP1B, and one molecule tested so far is trodusquemine and has shown impact on this specific enzyme. More research continues on finding compounds that can target a key component in the anxiety cycle and provide better alternatives to treating chronic stress.

For more reading:

*"Helping Brains Relieve Anxiety" by Michael Torrice, Chemical & Engineering News, News of the Week, Vol. 93, Issue 10, p 5
 *"Chronic Stress Induces Anxiety via an Amygdalar Intracellular Cascade that Impairs Endocannabinoid Signaling" by Z. Qin, X. Zhou, N.R. Pandey, H.A. Vecchiarelli, C.A. Stewart, X. Zhang, D.C. Lagace, J.M. Brunei, J.C. Beique, A.F. Stewart, M.N. Hill, H.H. Chen
*"Coordinated Regulation of Insulin Signaling by the Protein Tyrosine Phosphatases PTP1B and TCPTP" by S. Galic, C. Hauser, B.B. Kahn, F.G. Haj, B.G. Neel, N.K. Tonks, and T. Tiganis

Out of Sight, Out of Mind: Fixing Our Culverts and Sewers

Do you ever wonder what those large pipes by the side of the road are for? 

Typically culverts are made of metal and concrete.

 (image from http://www.specialtysupply.com/storm-water-management/)

These are culverts and used for allowing water to pass under a road, driveway, or embankment. Without them, we would literally be in deep water during the next vigorous rainstorm. Part of our ability to maintain a safe and comfortable lifestyle lies in the presence of these large pipes as well as sewer lines which carry away our wastes for further dispatch.

 

Newer sewer pipes can be made of concrete or polyvinyl chloride. Older ones can be made of clay and will last up to ~50 years. 
(image by Eric Gaertner http://blog.mlive.com/chronicle/2008/0/laketon_township_sewer_water_p.html)

Besides the passage of time, factors such as ground movement, soil conditions, random tree roots, and even ground excavation for street repair can cause corrosion or damage to these pipes, and they have to be either repaired or replaced. For a homeowner in Denver, CO, replacing a sewer main can be costly: anywhere from $3,300 to as high as $17,000.

 (image from Karen Schneider, http://coloradodenverinsuranceagent.com/2011/06/20/will-my-home-insurance-company-pay-for-a-new-sewer-line/)

One technology that is more cost-effective and preferred over replacement is CIPP or "Cured-In-Place-Pipe". It was invented in the early 1970s by Eric Wood, an English agricultural engineer, who took a flexible plastic and felt liner and impregnated it with a polymeric resin (either epoxy, polyester, or polyurethane). Placing this inside the sewer line he was trying to repair, he let the material cure in a matter of hours and presented a trenchless solution.

Here are 2 YouTube videos about CIPP. The first is an animation of what is involved in its installation. The second shows an actual installation in the field.  

 

CIPP (Cured In Place Pipe) Demonstration - Advanced Pipe Repair

A Tech Sewer CIPP

“The CIPP program is also far less expensive than replacing sewer mains. Using this technology costs the Service Authority roughly $31 a foot, which costs around four times less than constructing a foot of new sewer main," said James McCarroll who is the Inflow and Infiltration Supervisor of the Prince William County Service Authority in northern Virginia.

With the advantages that CIPP provides - no need to dig, shorter timeframe, minimal shutoff of water service, and cheaper cost - we would consider this an ideal solution. But a number of concerns have been raised about the use of styrene which is one of the co-monomers in the resin itself as well as detectable amounts of other chemicals after curing. Hot water or steam is typically used to cure the resin for several hours, and the water would be discharged through the culvert without any processing.

In a 2014 published paper in Environmental Science and Technology, M. L. Tabor, D. Newman, and A. J. Whelton collected condensate after the curing process and analyzed it for aquatic toxicity. One way of determining toxicity was to place some Daphnia magna (a freshwater water flea) in this water:

 a female adult Daphnia magna

(image by Hajime Watanabe (PLoS Genetics, March 2011) [CC BY 2.5 (http://creativecommons.org/licenses/by/2.5)], via Wikimedia Commons

Within 24 hours, they dissolved! Even after diluting by a factor of 10,000 the water fleas still had 100% mortality within 48 hours. Besides styrene, numerous other chemicals were detected that originated from uncured resin, plasticizers, and initiator byproducts. After 35 days some were still detectable.

Note: the red highlighted parts indicate where the monomers react to form polymers.

In a literature review conducted by A. J. Whelton et al., CIPP technology between 2004 and 2010 caused severe enough environmental consequences to result in hospital evacuations and fish kills.
In some cases, its use was temporarily halted.

In response, resin manufacturers like Interplastic Corporation and AOC Resins have developed non-styrene alternatives involving epoxy or vinyl toluene. In other cases, UV-radiation was used instead of hot water or steam in the curing process. There still remains a need to investigate the immediate environmental impact of discharging a large quantity of unremediated curing water. At this time there is no industry-accepted standard procedure that treats or sets the limits on CIPP chemicals to be discharged into the environment.

(image by Jim Rush of Trenchless Technology)

Precision Industrial Maintenance Inc. (PIM) was subcontracted to repair culverts in

Upstate New York. Ultraviolet radiation can be used instead of hot water or steam

in CIPP resin curing.

For more information:

*StormDrain Patching Method Poses Environmental Risks; Chemical & Engineering News, Volume 93, Issue 17 (April 27, 2015)

*Liquid Assets - The Story of Our Water Infrastructure

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)