Hardly Ever Update
So...I don't know why, I never update I never do anything any more. I am in Physics right now and I wish I was somewhere else. Thank GOD it's going to be my last term of it (hopefully)
Next year I get the good stuff.
Pharmaceutics I, Physiology/Pathophysiology I,Biochemistry,Immunology, and an elective.
This summer I really want to continue horseback riding because I've become totally obssessed. I got to canter for the first time (well, the first time that Chrissy [my instructor] let me that is). But I also need to work so that I can pay mad billz style.
For the second half of the summer if all goes well *crosses fingers* I'll be back in albany working on my summer stipend thing.
Specific Aim 1: To synthesize two α-tocopherol-lipoic acid derivates
Recent studies have shown promise in α-tocopherol-lipoic acid derivates. Preliminary studies have shown α-T-lipoic acid to have increased in vitro activity. The goal of the experiment is to link the lipoic acid with α-T through two different bonds. The links will provide the amide and urethane target molecules.
Amide Analog Synthesis Compound 1
The synthesis of the amide analog cannot occur without first creating the proper starting materials. Commercial α-tocopherol and lipoic acid can be converted to these materials through multi-step syntheses. In the proposed synthesis the target molecules are obtained by first treating α-tocopherol with NaOH then treating it with (EtO)2POCl. This converts α-tocopherol into its respective aryl diethylphosphate. Treating the aryl
Figure 1: Amide Analog
diethylphosphate with KNH2, and then reacting it with NH3 creates it’s respective amine. Lipoic acid can be converted to its respective acid chloride through the use of SOCl2. Finally the α-tocopherol and lipoic acid derivatives are then reacted to form the target molecule.
Urethane Analog Synthesis Compound 2
The synthesis of the urethane analog also requires the transformation of the lipoic acid. Lipoic acid will be converted into its isocyanate analog through a series of reactions.The first step of the reaction involves treating lipoic acid with cyanobromide (BrCN). This produces the the nitrile derivative of lipoic acid. This species is then reduced to its amino equivalent through the use of catalytic hydrogenation or lithium aluminum hydride. However these conditions are also
Figure 2: Urethane Analog
likely to reduce the disulfide to it’s sulfhydryl derivative. Therefore the second step of the reaction calls for oxidation through the use of H2O2.This species will then be reacted with Trichloromethylchloroformate to form a chloroformamide. This species is pseudo-intermediate in that it will decompose to form HCl and the isocyanate lipoic acid analog. It is this compound which will react with α-tocopherol to form the target urethane analog.
Specific Aim 2: To evaluate in vitro antioxidant activity of synthesized α-tocopherol-lipoic acid compounds
The in vitro antioxidant activity of the two synthesized compounds will be evaluated by measuring each compound’s effect on the inhibition of ferrous ion-stimulated formation of maliondialdehyde (MDA). This is an end product of lipid peroxidation in rat liver microsomes. The in vitro antioxidant activity of each compound will be compared with the in vitro antioxidant activity of α-tocopherol, lipoic acid and the original α-tocopherol-lipoic acid compound.
Project Activities:
Throughout the eight weeks two compounds will be synthesized and tested for their in vitro antioxidant activity. According to the proposed timeline by Dr. Hass, four compounds should take one to three months to synthesize. Half the amount of compounds should take two to six weeks. The compounds will be synthesized according to the outline above. The synthesis may require appropriate adjustment. This will require proper literature review. The in vitro antioxidant activity will be tested as outlined in specific aim 2.
Project Timeline:
Weeks Experiments
1-6 Synthesis of compounds 1& 2
1-6 Literature review for synthesis of compounds 1 & 2
3-8 Evaluation/comparison of antioxidant activity of compounds 1, 2
Reason for Applying to Program
Research chemistry takes a lot of knowledge of basic principles and a little luck. A good chemist knows when to recognize when something is worth looking at. This is the hallmark of a veteran scientist: knowing how to apply their curiosity. Chemistry has always been a passion of mine. A good chemist should always be curious. I have always been a naturally curious person, especially when it comes to chemistry. The summer stipend program will be a wonderful opportunity to focus my curiosity to understand what I should be curious about.
Furthermore, I feel like I am a minority at Albany College of Pharmacy who would like to do pharmaceutical research. This program will give me the ability to conduct research and provide invaluable experience. It is this experience that will distinguish me from other graduates who would potentially apply for the pharmaceutical research positions.
This project would be feasible for me to do. However I do feel that it will present somewhat of a challenge. This is so because in the lab synthesis reactions are well defined and tailored for an educational purpose. However in true research things are not likely to go as smoothly as one would want. This would be the first time that I would have to actually modify the procedures myself. To do research like this would be to fulfill a lifelong dream of mine.
Expected Outcome from Experience
The expected outcome of the experiment is to support the hypothesis that these synthesized compounds have increased in vitro antioxidant activity. Results of the experiment milestones shall be reported to the scientific community through poster presentations or scientific conferences (i.e. American Chemical Society) and journal publications.
Beyond the summer I hope to continue working on this experiment as an independent study during the school year. Ultimately I would like to help in the in vivo analysis and help to design a pharmaceutical agent. I hope that this summer will be the beginning of a life long research career. In these 8 weeks I aspire to grow greatly both as a person and as a scientist.
miss brooklyn like crazy
Next year I get the good stuff.
Pharmaceutics I, Physiology/Pathophysiology I,Biochemistry,Immunology, and an elective.
This summer I really want to continue horseback riding because I've become totally obssessed. I got to canter for the first time (well, the first time that Chrissy [my instructor] let me that is). But I also need to work so that I can pay mad billz style.
For the second half of the summer if all goes well *crosses fingers* I'll be back in albany working on my summer stipend thing.
Specific Aim 1: To synthesize two α-tocopherol-lipoic acid derivates
Recent studies have shown promise in α-tocopherol-lipoic acid derivates. Preliminary studies have shown α-T-lipoic acid to have increased in vitro activity. The goal of the experiment is to link the lipoic acid with α-T through two different bonds. The links will provide the amide and urethane target molecules.
Amide Analog Synthesis Compound 1
The synthesis of the amide analog cannot occur without first creating the proper starting materials. Commercial α-tocopherol and lipoic acid can be converted to these materials through multi-step syntheses. In the proposed synthesis the target molecules are obtained by first treating α-tocopherol with NaOH then treating it with (EtO)2POCl. This converts α-tocopherol into its respective aryl diethylphosphate. Treating the aryl
Figure 1: Amide Analog
diethylphosphate with KNH2, and then reacting it with NH3 creates it’s respective amine. Lipoic acid can be converted to its respective acid chloride through the use of SOCl2. Finally the α-tocopherol and lipoic acid derivatives are then reacted to form the target molecule.
Urethane Analog Synthesis Compound 2
The synthesis of the urethane analog also requires the transformation of the lipoic acid. Lipoic acid will be converted into its isocyanate analog through a series of reactions.The first step of the reaction involves treating lipoic acid with cyanobromide (BrCN). This produces the the nitrile derivative of lipoic acid. This species is then reduced to its amino equivalent through the use of catalytic hydrogenation or lithium aluminum hydride. However these conditions are also
Figure 2: Urethane Analog
likely to reduce the disulfide to it’s sulfhydryl derivative. Therefore the second step of the reaction calls for oxidation through the use of H2O2.This species will then be reacted with Trichloromethylchloroformate to form a chloroformamide. This species is pseudo-intermediate in that it will decompose to form HCl and the isocyanate lipoic acid analog. It is this compound which will react with α-tocopherol to form the target urethane analog.
Specific Aim 2: To evaluate in vitro antioxidant activity of synthesized α-tocopherol-lipoic acid compounds
The in vitro antioxidant activity of the two synthesized compounds will be evaluated by measuring each compound’s effect on the inhibition of ferrous ion-stimulated formation of maliondialdehyde (MDA). This is an end product of lipid peroxidation in rat liver microsomes. The in vitro antioxidant activity of each compound will be compared with the in vitro antioxidant activity of α-tocopherol, lipoic acid and the original α-tocopherol-lipoic acid compound.
Project Activities:
Throughout the eight weeks two compounds will be synthesized and tested for their in vitro antioxidant activity. According to the proposed timeline by Dr. Hass, four compounds should take one to three months to synthesize. Half the amount of compounds should take two to six weeks. The compounds will be synthesized according to the outline above. The synthesis may require appropriate adjustment. This will require proper literature review. The in vitro antioxidant activity will be tested as outlined in specific aim 2.
Project Timeline:
Weeks Experiments
1-6 Synthesis of compounds 1& 2
1-6 Literature review for synthesis of compounds 1 & 2
3-8 Evaluation/comparison of antioxidant activity of compounds 1, 2
Reason for Applying to Program
Research chemistry takes a lot of knowledge of basic principles and a little luck. A good chemist knows when to recognize when something is worth looking at. This is the hallmark of a veteran scientist: knowing how to apply their curiosity. Chemistry has always been a passion of mine. A good chemist should always be curious. I have always been a naturally curious person, especially when it comes to chemistry. The summer stipend program will be a wonderful opportunity to focus my curiosity to understand what I should be curious about.
Furthermore, I feel like I am a minority at Albany College of Pharmacy who would like to do pharmaceutical research. This program will give me the ability to conduct research and provide invaluable experience. It is this experience that will distinguish me from other graduates who would potentially apply for the pharmaceutical research positions.
This project would be feasible for me to do. However I do feel that it will present somewhat of a challenge. This is so because in the lab synthesis reactions are well defined and tailored for an educational purpose. However in true research things are not likely to go as smoothly as one would want. This would be the first time that I would have to actually modify the procedures myself. To do research like this would be to fulfill a lifelong dream of mine.
Expected Outcome from Experience
The expected outcome of the experiment is to support the hypothesis that these synthesized compounds have increased in vitro antioxidant activity. Results of the experiment milestones shall be reported to the scientific community through poster presentations or scientific conferences (i.e. American Chemical Society) and journal publications.
Beyond the summer I hope to continue working on this experiment as an independent study during the school year. Ultimately I would like to help in the in vivo analysis and help to design a pharmaceutical agent. I hope that this summer will be the beginning of a life long research career. In these 8 weeks I aspire to grow greatly both as a person and as a scientist.
miss brooklyn like crazy