This is just an fyi for those still studying:
C=O absorbs around 1700cm-1, C-O 1100cm-1
O-H absorbs around 3450cm-1
C=O for ketone is approx 1720 and carboxylic acid approx 1740cm-1. For esters, also look for bands at 1050 and 1250cm-1.
C triple bond C - 2100cm-1, C=C 1650cm-1, and C-C 1300- 800cm-1
C triple bond N- 2200cm-1, C=N 1600cm-1 and C-N 110cm-1
Hydrogens attached to sp carbon will show a stretch at 3300cm-1, hydrogen attached to sp2 will show a stretch around 3100cm-1, and sp3 carbon bonded to a hydrogen will show a stretch around 2900cm-1.
Aldehyde also show two bands at 2820 and 2720cm-1
The O-H absorption in carboxylic acids will show a broad peak at 3300- 2500cm-1.
N-H shows a narrower peak which is more intense at 3300cm-1
Absence at 720 indicate that a compound has fewer than CH2 groups.
Absorption band at 980 indicates a trans.
Hope these helps!
Good luck tomorrow.
Sunday, May 5, 2013
Last minute study guide question
I have one more question from the ACS guide im hoping some one can help me out with; i know its late. On the stereochemistry section problem 23, they are asking about which compounds are optically active and I cant even find a stereocenter in any of them. Maybe im just overlooking something but I cant see how the answer they give can be correct. Thanks,
Mechanism: Ozonolysis
Unfortunately, my computer had technical difficulties with ChemDraw. So, I had to do it the old-fashioned way and draw the mechanism by hand. I chose to do ozonolysis, a mechanism we briefly discussed in our final class period. It uses Ozone (O3), Zinc and H2O. Zinc is actually used to to reduce the hydrogen peroxide which is generated in the hydrolysis of the ozonide intermediate. This rxn is fairly easy to remember. You cleave at the alkene and add two carbon-oxygen double bonds at that "cut". Below I have included the mechanism:
Friday Seminar
There was 5 presentations during the seminar last Friday. And I am going to talk about the first presentation of Jamie Tran. Her presentation was about "Inhibitory effects of iodide, azide, and nitrite ions on photosystem II under illumination."
She start out with an introduction about Photosystem II. In photosystem II, chloride ion was needed to activate the oxygen process in MN-cluster complex, but how? The purpose is to characterize the binding sites of chloride ions on photosytem 2 and to examine how iodide, azide, and nitrite ions donate electrons through MN4CaO5 cluster or Tyrosine.
Her hypothesis was that she thought those ions would reduce the site of oxygen evolution by donating electron.
In the experiment process, she did oxygen evolution assay and evaluate the activity of azide, iodide, and nitrite on NaCl washed PSII under Illumination and in the dark in 5 minute incubation. The result was the irreversible damage by N3, I and NO2 ions.
In the next experiment, it was the process of electron transfer in Tris-washed photosystem 2. The result was that there was electron donation of iodide,nitrite and azide in the dark and under illumination in Tris-washed.
And the last one is about electron donating of Azide without the presence of PSII. The result was that the electron donation of azide was more significant with the presence of the tris-washed PSII under illumination. Also the electron donation of azide occurred similarly regardless if you use Tris-washed in the dark.
Conclusion: The electron transfer to PSII from the anion was absent or very small. The damage occurs within just a few catalyst turnover, so electron transfer is not significant.
She start out with an introduction about Photosystem II. In photosystem II, chloride ion was needed to activate the oxygen process in MN-cluster complex, but how? The purpose is to characterize the binding sites of chloride ions on photosytem 2 and to examine how iodide, azide, and nitrite ions donate electrons through MN4CaO5 cluster or Tyrosine.
Her hypothesis was that she thought those ions would reduce the site of oxygen evolution by donating electron.
In the experiment process, she did oxygen evolution assay and evaluate the activity of azide, iodide, and nitrite on NaCl washed PSII under Illumination and in the dark in 5 minute incubation. The result was the irreversible damage by N3, I and NO2 ions.
In the next experiment, it was the process of electron transfer in Tris-washed photosystem 2. The result was that there was electron donation of iodide,nitrite and azide in the dark and under illumination in Tris-washed.
And the last one is about electron donating of Azide without the presence of PSII. The result was that the electron donation of azide was more significant with the presence of the tris-washed PSII under illumination. Also the electron donation of azide occurred similarly regardless if you use Tris-washed in the dark.
Conclusion: The electron transfer to PSII from the anion was absent or very small. The damage occurs within just a few catalyst turnover, so electron transfer is not significant.
The Synthesis of Propofol and Similar Analogs
The use of anesthetics can be traced back to Ancient Sumeria and have been written about in the texts of civilizations such as the Greeks and Romans. However, it wasn't until the 19th Century that General Anesthesia came into fruition. The first recorded use was at Massachusetts General Hospital in 1846. Dr. John Collins Warren used diethyl ether, commonly known as ether, as an inhalation anesthetic. Unfortunately, ether was complicated by its slow effects and unpleasant recovery period.
The next development in General Anesthesia did not occur until the 20th Century. Intravenous anesthetics had been widely avoided because they caused complications involving the obstruction of the airway. However, these complications were greatly minimized with the invention of the laryngoscope in 1913 by Chavalier Jackson.
In 1934, Sodium pentothal (also known as Thiopental sodium) was synthesized by Ernest Volwimer and Donalee Tabern of Abbott Laboratories and was administered intravenously by Ralph Waters on March 8, 1934. Unlike it's predecessors, Sodium pentothal caused almost immediate loss of consciousness and had a much shorter recovery period. However, it's major drawback was dosage. Ironically, the effective dose was 75% of the lethal dose.
Today, the most commonly used intravenous anesthetic is Diprivan (better known as Propofol) because it can be administered quickly and effectively and has a very large margin of safety. In fact, the demand for Propofol throughout the medical community has been so great that suppliers such as Hospira, Teva, AstraZeneca have not been able to keep up. As a result, in recent months the FDA has been forced to approve and import similar drugs such as Propoven (See article here).
In recent news, pharmaceutical companies have been developing similar analogs of Propofol to help resolve national shortages. One such company is Abraxis BioScience, which is a subsidiary of Celgene Coporation (The patent and publication from Celgene can be found here.)
As outlined in their patent, the current method of producing these analogs is by treating a mixture of 2,6-dialkyl phenol with acyl chloride in the presence of aluminum chloride for 24 hours:
This mechanism is known as Friedel-Crafts Acylation and proceeds as follows:
Sources:
The next development in General Anesthesia did not occur until the 20th Century. Intravenous anesthetics had been widely avoided because they caused complications involving the obstruction of the airway. However, these complications were greatly minimized with the invention of the laryngoscope in 1913 by Chavalier Jackson.
In 1934, Sodium pentothal (also known as Thiopental sodium) was synthesized by Ernest Volwimer and Donalee Tabern of Abbott Laboratories and was administered intravenously by Ralph Waters on March 8, 1934. Unlike it's predecessors, Sodium pentothal caused almost immediate loss of consciousness and had a much shorter recovery period. However, it's major drawback was dosage. Ironically, the effective dose was 75% of the lethal dose.
Today, the most commonly used intravenous anesthetic is Diprivan (better known as Propofol) because it can be administered quickly and effectively and has a very large margin of safety. In fact, the demand for Propofol throughout the medical community has been so great that suppliers such as Hospira, Teva, AstraZeneca have not been able to keep up. As a result, in recent months the FDA has been forced to approve and import similar drugs such as Propoven (See article here).
In recent news, pharmaceutical companies have been developing similar analogs of Propofol to help resolve national shortages. One such company is Abraxis BioScience, which is a subsidiary of Celgene Coporation (The patent and publication from Celgene can be found here.)
As outlined in their patent, the current method of producing these analogs is by treating a mixture of 2,6-dialkyl phenol with acyl chloride in the presence of aluminum chloride for 24 hours:
This mechanism is known as Friedel-Crafts Acylation and proceeds as follows:
Sources:
- http://www.webmd.com/pain-management/features/propofol-faq
- http://en.wikipedia.org/wiki/History_of_general_anesthesia#20th_century
Saturday, May 4, 2013
Undergraduate Research Symposium
The last chemistry seminar of the semester was on Friday. Five undergraduate students presented their research and one of them was our SIP leader Barrett Honeycutt! In SIP he mentioned he would be presenting his research at the seminar, and when he showed up in class on Friday wearing a snazzy suit, I knew I couldn't miss it.
Barrett has been doing research with Dr. Petersen, and at the final SIP session Barrett said he will be employed by her lab full time starting next semester. On Monday of this week, Dr Petersen talked with us in class about her research a bit, but she focused mainly on her goal of synthesizing small chemical building blocks with chiral stereocenters which can be used to synthesize larger molecules of medical importance.
At the seminar Barrett presented third, and from what I heard, the research that he has been doing in Dr Petersen's lab did not involve any stereocenters, but instead involved substituting an aromatic compound with COOH groups. The commercially available aromatic compound they were starting with was:
They wish to synthesize each of these three molecules:
Once those compounds are synthesized they will be shipped to Virginia Tech so that they may be used in the construction of semiconductors. The collaborator at Virginia Tech who needs these compounds is a friend of Dr Petersen's from graduate school.
Dr Petersen explained the specifics of the semiconductors to me after the seminar, but I'm afraid most of it was over my head. MOFs (Metal Organic Frameworks) were mentioned during Barrett's talk, and online I found some references to MOFs being used as semiconductors, so it may be that these compounds they are creating will act as ligands in metallic compounds like the ones we worked with in chapter 11. Speculation aside, there is reason to believe that molecules like those shown above will have qualities useful in the production of semiconductors, and once they are isolated, they will be tested at to see if they function as expected.
As of last Friday, the first compound with the COOH groups substituted para on the second ring of tetracene had been successfully created. It was a rust colored solid. The other two compounds have not yet been made. Barrett proposed a mechanism but he sped through it too fast for me to copy it down. Sorry! There was a bridge formed between the two carbons on ring two of tetracene, perhaps with a Diels-Alder reaction. Once the bridge was formed across the two desired carbons, it could be treated with an oxidizing agent which would lead to the desired carboxyl groups. (I'm working from memory here, so I'm sure there will be some corrections from Dr Petersen in the comments.)
The following compound was used for something, but I'm not sure what it was, and I couldn't find any information about it online:
When creating that first molecule, Barrett put some reagents together, and then left them in the microwave for 30 hours. (There was some laughter at the top of the room at this part, but Barrett stared them down like he didn't see what was so funny.) Along with the desired compound, an impurity was formed. I think the impurity was substituted twice, on both ring 2 and 3. Barrett worked hard to remove that impurity, and there was a 77% yield. After this there was a reflux with 40% NaOH at 120 degrees Celsius for 2 hours. Oxidative cleavage (or splitting the bridge) was carried out using periodinane. Then Pinnick oxidation was used to form the carboxyl groups.
Dr Petersen and Barrett are trying to manage the workup so that yield and purity will be improved. There were a few helpful suggestions from the audience after Barrett's presentation.
Because this summary is already getting way too long, I'll include descriptions of the other four undergraduate research presentations in the comments of this post if anyone is interested.
-EK
Barrett has been doing research with Dr. Petersen, and at the final SIP session Barrett said he will be employed by her lab full time starting next semester. On Monday of this week, Dr Petersen talked with us in class about her research a bit, but she focused mainly on her goal of synthesizing small chemical building blocks with chiral stereocenters which can be used to synthesize larger molecules of medical importance.
At the seminar Barrett presented third, and from what I heard, the research that he has been doing in Dr Petersen's lab did not involve any stereocenters, but instead involved substituting an aromatic compound with COOH groups. The commercially available aromatic compound they were starting with was:
They wish to synthesize each of these three molecules:
 |
| These are drawn from memory, so please correct me if I got them wrong! |
Once those compounds are synthesized they will be shipped to Virginia Tech so that they may be used in the construction of semiconductors. The collaborator at Virginia Tech who needs these compounds is a friend of Dr Petersen's from graduate school.
Dr Petersen explained the specifics of the semiconductors to me after the seminar, but I'm afraid most of it was over my head. MOFs (Metal Organic Frameworks) were mentioned during Barrett's talk, and online I found some references to MOFs being used as semiconductors, so it may be that these compounds they are creating will act as ligands in metallic compounds like the ones we worked with in chapter 11. Speculation aside, there is reason to believe that molecules like those shown above will have qualities useful in the production of semiconductors, and once they are isolated, they will be tested at to see if they function as expected.
As of last Friday, the first compound with the COOH groups substituted para on the second ring of tetracene had been successfully created. It was a rust colored solid. The other two compounds have not yet been made. Barrett proposed a mechanism but he sped through it too fast for me to copy it down. Sorry! There was a bridge formed between the two carbons on ring two of tetracene, perhaps with a Diels-Alder reaction. Once the bridge was formed across the two desired carbons, it could be treated with an oxidizing agent which would lead to the desired carboxyl groups. (I'm working from memory here, so I'm sure there will be some corrections from Dr Petersen in the comments.)
The following compound was used for something, but I'm not sure what it was, and I couldn't find any information about it online:
When creating that first molecule, Barrett put some reagents together, and then left them in the microwave for 30 hours. (There was some laughter at the top of the room at this part, but Barrett stared them down like he didn't see what was so funny.) Along with the desired compound, an impurity was formed. I think the impurity was substituted twice, on both ring 2 and 3. Barrett worked hard to remove that impurity, and there was a 77% yield. After this there was a reflux with 40% NaOH at 120 degrees Celsius for 2 hours. Oxidative cleavage (or splitting the bridge) was carried out using periodinane. Then Pinnick oxidation was used to form the carboxyl groups.
Dr Petersen and Barrett are trying to manage the workup so that yield and purity will be improved. There were a few helpful suggestions from the audience after Barrett's presentation.
Because this summary is already getting way too long, I'll include descriptions of the other four undergraduate research presentations in the comments of this post if anyone is interested.
-EK
Seminar: Mutant Mu-Opiod Receptors and Pain Management
On May 3rd,
I had the opportunity to attend Elizabeth Pearsall’s thesis presentation
entitled: Molecular
Mechanisms of Mutant Mu Opioid Receptors (MOR) where Naloxone, an Inverse
Agonist, Acts as an Agonist and Relieves Pain . The purpose of her
dissertation was to shed light on the 100 million Americans who suffer from chronic
pain, a population of people that totals more than all other conditions combined
(diabetes, heart disease etc.). Consequently, pain management is an aspect that
has caused difficulty for those individuals who experience chronic and acute
pain on a daily basis. Although there are painkillers available now for such
patients, these medications include many unavoidable side effects such as,
respiratory depression, gastrointestinal problems like constipation, as well as
dependence, addiction, and withdrawal symptoms. Therefore, Pearsall and Dr.
Reggio’s lab focused on the mu-opiod receptor agonist (morphine) and its sister
drugs such as codeine, oxycodone etc. in efforts to discover the mechanism of a
mutant mu-opioid that managed pain with
less tolerance and withdrawal than the current market drugs.
In
fact, there are three types of opioid receptors, including delta and kappa.
However, only mu agonists produce analgesic effects. Pearsall, used Naxolone, a
drug used in the contest the effects of drug overdoses, to study its molecular
mechanism as a full agonist and a partial agonist. It was important to note
that in its regular form, Naxolone acts an antagonist, defined as a receptor drug
that does not provoke a biological response itself upon binding to a receptor,
but blocks or dampens agonist-mediated responses*. Essentially, as a single mutant
MOR, Naxolone preformed as a partial agonist, whereas in the triple mutant form
(TMT), Naxolone acted as a full agonist. As an agonist, Naxolone, therefore,
takes on a different task than its original function, instead binding to a cell
receptor and directly triggering a response by that cell.
Experimentally,
the mutant MOR of naxolone was injected into mice between their vertebrae and
spine via a targeted-gene therapy strategy. The effects were quite
ground-breaking, providing localized pain management for the mice for 8 weeks! The
localization of the pain management was pivotal, in that, if an individual
needed another drug elsewhere in the body, the MOR would not interact with it. Whereas,
in a drug with systemic effects, another drug introduced to the body could
possibly produce counter effects or cause a harmful/deadly interaction. If you
want to read up on more about Naxolone and strides towards pain management,
check out these cited sources below.
*www.fda.gov/drugs
1. Chen,
S. L.; Ma, H. I.; Han, J. M.; Tao, P. L.; Law, P. Y.; Loh, H. H., dsAAV type
2-mediated gene transfer of MORS196A-EGFP into spinal cord as a pain management
paradigm. Proc Natl Acad Sci U S A 2007, 104 (50), 20096-101.
2. Kao,
J.; Chen, S.; MA, H.; Law, P. Y.; Tao, P. L.; Loh, H. H., Intrathecal delivery
of a mutant Mu-opioid receptor activated by naloxone as a possible
antinociceptive paradigm. The Journal of Pharmacology and Experimental
Therapeutics 2010, 334 (3), 739-45.
3. Claude-Geppert,
P. A.; Liu, J.; Solberg, J.; Erickson-Herbrandson, L. J.; Loh, H. H.; Law, P.
Y., Antagonist efficacy in MORS196L mutant is affected by the interaction
between transmembrane domains of the opioid receptor. J Pharmacol Exp Ther
2005, 313 (1), 216-26.
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