All the work done these previous semesters were showed and explained in the Biominds Research Day, where 100 students of five campus of the University of Puerto Rico demonstrated that this generation is full of excellent and intelligent persons with the power to change the world.  As part of the activity we visited three other posters to analyze them.

             The first poster I went to see was the one of Glorivee Hernandez Garcia of the University of Puerto Rico in Humacao. She works analyzing and comparing the physiology and the diverse environments of the bacteria Bacillus subtilis that generates crystals. This quality is important because of its relationship with the development of kidney stones that affects many people and the role in the architecture as a solution for the restoration of historic monuments. She did a great job and I am impressed that bacteria cause so many things that have an effect on the earth just to have this quality as well as many others.

            The second poster was the one of Abby J. Agosto of the UPR of Río Piedras. This investigation was complex because it is not a recent investigation. The material presented has several years in process and therefore her work is much more advanced than others. She works with the mechanisms and interactions that need to occur for the expression of a gene. She analyzed the interaction between the proteins Mex67p and Upf1p to show that they facilitate the mRNA translation that is need for the migration outside the nucleus. Her work was very high-quality and has a very formal way of communicating. It was an outstanding work!

            The last poster was the one of Verónica Román of the UPR of Humacao. She works with an unknown type of bacterium that helps control the smell of decomposing faeces of cattle on ranches. This bacterium has the characteristic of changing color in anaerobic environments. Besides that quality it was needed the further investigation of the composition of these waters. What I liked about this work is that her explanation was brilliant because she becomes something that seems difficult very easy.

            This is my last post for the BIOMINDS program. Thanks for all the opportunities offered which I lived to the fullest. To all the people that influenced my work thank you for your patience and effort. I wish success to all students participating in this program and I hope that you can achieve your goals.

            This month was really good for our investigation because we finally got the results of the elemental analysis of my compounds with benzothiazoles ligands and they show a difference of less than 0.5 % with the theoretical values demonstrating the purity of the complexes.  Now that we are completely sure that the syntheses are done we are going to proceed to know their activity in cancer cells line. Our major problem is the time. To do this stuff we need a lot of time that sometimes is very difficult to have because of our classes. The second problem is that the quantity of the samples is not enough to make several analyses and we may do them once more passing through the process of characterization again. To reduce these problems we are working in group and helping each other to have things on time and using the minimum of sample necessary for the tests we will be working on.  In the scale of progress I believe that my research is right now in a 3, because a five will be show their reactivity comparing with cisplatin.

Abstract:

 Platinum complexes have been a subject for the development of drugs to treat certain kinds of cancer. Cisplatin, cis-[PtCl₂(NH₃)₂] is successfully used in chemotherapy, and the new drug picoplatin, cis-[PtCl₂(NH₃)(2-methylpyridine)] has shown evidence of antitumor activity in cisplatin-resistant cells. The purpose of this experiment is to develop new compounds structurally related to picoplatin, using the mixed-amine system: NH₃/benzothiazole.  The change in the amine 2-methylpiridine and the addition of methyl groups to the benzothiazole ligand can have significant effects in the activity or toxicity of Pt compounds. The present experiment deals with the synthesis and characterization of mixed-amine compounds cis-[PtCl₂(NH₃)(L)], where L=1,3-benzothiazole, 2-methylbenzothiazole and 2,5,6-trimethylbenzothiazole.  The complexes were prepared by the direct reaction of an aqueous solution of K[PtCl₃(NH₃)] with an ethanol solution of the ligand.  The complexes cis-[PtCl₂(NH₃)(benzothiazole)] (1), cis-[PtCl₂(NH₃)(2-methylbenzothiazole)] (2) and cis-[PtCl₂(NH₃)(2,5,6-trimethylbenzothiazole)] (3) were characterized by ¹H nuclear magnetic resonance (500 MHz, in DMF-d₇) and infrared spectroscopy.  The infrared bands characteristics of the amine group, the methyl groups (in complexes 2 and 3) and the benzothiazole ligand are present in the spectra and will be presented. The ¹H NMR spectrum of 1 shows the aromatic protons of coordinated benzothiazole: a singlet at 9.975 ppm, assigned to H(2), doublets at 8.3 ppm and 9.0 ppm, assigned to H(4) and H(7); and triplets at 7.78 ppm and 7.657 ppm, corresponding to H(5) and H(6). The broad signal at 4.47 ppm corresponds to the ammine group. The spectrum of the complex with 2-methylbenzothiazole (2) was also recorded. The doublets at δ=8.17 ppm and δ=9.12 ppm are assigned to H(4) and H(7), the triplets at 7.61 ppm and 7.73 ppm correspond to H(5) and H(6). The resonance at 3.36ppm is due to the protons of the methyl group in the second position of the molecule.  The broad signal at 4.39 ppm is the signal of the NH₃. The ¹H NMR spectrum of the complex with 2,5,6-trimethylbenzothiazole (3) also shows the aromatic protons: the doublets at δ=8.88 ppm and δ=7.87ppm are due to H(4) and H(7), the peaks at 2.42 ppm, 2.49ppm and 3.31ppm correspond to the protons of the methyl groups attach to the sixth, fifth and second carbon atoms of the benzothiazole moiety. The broad signal positioned at 4.38 ppm is the signal of NH₃. The presence of the characteristic NH₃ band in all spectra confirms the mixed ligand nature of the new compounds.   The spectral studies confirm that the synthesis was successful, and the products mainly consist of the desired cis-[PtCl₂(NH₃)(2-methylbenzothiazole)], cis-[PtCl₂(NH₃)(2,5,6-trimethylbenzothiazole) and cis-[PtCl₂(NH₃)(benzothiazole)] complexes.

We finally made it to the last semester of the Biominds Program and I have to say that it will be an experience I will never forget. There is lots of work to do and so little time. During this semester of investigation I will work on: Characterization and Interactions. After synthesizing the complexes with benzothiazole derivatives, we need to characterize (indentify) if the compound is in fact the complex of interest. After doing this we will interact the compounds, to see their reaction in a biological system. The main goals of this semester are: – Demonstrate that the two syntheses of the complexes with the ligands 2-methylbenzothiazole and 2,5,6-trimethylbenzothiazole are uncontaminated by making them Elemental Analysis (percent of carbon and hydrogen present in the molecule). – Purify the complex with the 1,3-benzothiazole to use it with the two other complexes to see how they react with the guanosine monophosphate and compare the same reaction but with cisplatin and 195Pt. This semester is a continuity of the same thing we were doing last semester with the only difference that this time the ligands that we are going to use are benzothiazoles with methyl groups. Right now one of the techniques that I want to develop is the recrystallisation to recover the first synthesis.

            From November 5^th to November 9^th I went to the minority conference ABRCMS on Orlando, Florida. It was a great professional and personal experience. I have the opportunity of meeting undergraduate and graduate students who were going to presents their work. I also met different professors that were offering us diverse possibilities of graduate and medical schools. The conferences were amazing but the two that I liked most were the one called “Targeting DNA-Adduct Stereochemistry and p53Mdm2 Complexes for Improved Breast Cancer Cell Death” by Dr. Jill Bargonetti because is very similar to my investigation in the way that she is working with the DNA bonding protein p53 that stops cell growth but it can induce cell death and “Choosing Sex: How Germ Cells Take the Road Less Traveled” by Dr. David C. Page. I choose this last one like my favorite because he explain that broad material in a very simply way and I really enjoyed it.  The booths were great. I took a lot of information and I even met Puerto Ricans studying in the United States.  But the thing that I liked the most was the Award time. Puerto Rico won a lot of awards and I felt very proud because of it. I will like to thanks Biominds and to my mentor, Mayra Cadiz, for giving me the opportunity of present my investigation.

         We reach to end of the second semester of investigation and I have to say that this was the best semester ever.  In contrast to the first semester of investigation this semester two platinum complexes with methyl groups in the benzothiazole were created. The complexes formed were cis-[PtCl₂(NH₃)(2,5,6-trimethylbenzothiazole)] and cis-[PtCl₂(NH₃)(2-methylbenzothiazole)]. The ¹H NMR spectral studies were made to confirm the creation of these complexes. Personally I am very satisfied because it’s very difficult to make these complexes and the NMR’s are looking good from my perspective. Now we need to make more studies to characterize these two syntheses and if they result to be uncontaminated we are going to study their reactions with guanosine monophosphate (GMP) and compare them to other syntheses created in the laboratory. Honestly, my investigation was not more that it was because I dedicated this semester to help creating other syntheses using different kinds of thiazole to present our investigation in the ABRCMS conference. But I don’t feel sorry for that because I learned more that I could think and I could see the difference of having a benzene stick together to the thiazole and what effects that brings to the complex. I want to thanks to my mentor, Dr. Mayra E. Cádiz, for be always available to answer questions and to help us in everything. To my lab partner, Magdelisse Velázquez, because she helped me in everything and we made in one semester something that other person could do in one year.

During the last weeks we have being creating new compounds with alkyl substituents in the thiazole and benzothiazole rings in order to evaluate the effect of the planar ligand in the activity and toxicity of these complexes. The complexes with the ligand 5-methylthiazole and 4,5-dimethylthiazole were characterized based on elemental analysis, IR and NMR. The complexes with the ligand 2-methylbenzothiazole and 2,5,6-trimethylbenzothiazole are still in the process of characterization.

     To develop a compound that destroys cancer cells effectively and that does not cause effects on the patient that affects its health while the disease is combat is our aspiration. Cisplatin and carboplatin were the most used drug to treat cancer but they were ineffective in some cases. Right now the scientists are working with one drug named Picoplatin that is very similar to our syntheses because it has a planar ligand (2-methylpyridine). We are going to be studying how these ligands react with DNA plasmids to see how effective they are.

                This semester the investigation has been easier that when we started. Now we know better the field we are investigating and everything is simpler. I took a conference about security in research laboratories given by Professor Robert Ríos. It was very cool take this chat with him because he was my professor Organic Chemistry. Right now I am helping my lab co-worker to make two thiazole synthesis with different alkyl substituents and then I will make another benzothiazole synthesis because I need to recover one that I left in solution. We are having trouble because the source of air we use to filtrate is corrupted. The mentor showed me another kind of filtrate using a special hose that use water to create air suction. At this precise moment I can tell that in the scale of progress my number is two. We are more focused in create more synthesis because we are hoping to present our results in ABRCMS (Annual Biomedical Research Conference for Minority Students) taking place in Orlando, Florida.

Another semester has begun. This is our second term of investigation sponsored by BioMinds. My three lab partners and I gave an oral report about what we have learned in our researches and what we are expecting to achieve. We all learned new things about each other’s researches. It was nice to see our mentor, Dr. Mayra Cádiz, so pleased about our results.

The goals that I am planning to reach on the end of the semester are:

1)     Recover a platinum complex that I left in the laboratory with the ligand 2,5,6-trymethylbenzothiazole and analyze it to see if the complex is present.

2)     With the created complex of cis-Pt(NH₃)Cl₂(benzothiazole) we will be making interacts with DNA plasmid.

3)     Make cis-Pt(NH₃)Cl₂(benzothiazole) synthesis with the K₂PtCl₄ and use the K[Pt(NH₃)Cl₂] only when is need it.  

Like the first semester will be doing synthesis and characterize them to know their reactions in the DNA. Now that we have more experience, the work is going to be easier. Right now, I am focusing in recuperate the last synthesis and is going to be made with some kind of new technique that the mentor is going to teach me. I am very excited and I know that this semester is going to be much better that the last one.

       This semester I have learned so many things and thanks to that I can say that this was a fantastic experience. At the beginning it was very hard but now is a very different thing. I will like to thanks my research mentor, Dr. Mayra Cádiz, because she was always there for me and she trusted me this difficult work and to my lab partner, Magdelisse, that helped me in some many things and never doubted of my work.

The synthesis is done but now is the time to know what effects would have in the plasmid DNA. This semester we could not make it because we did not have the plasmid DNA but I have faith that the next semester our investigation will be based on that.  

The only thing I could wish is to do the same synthesis but with the K₂PtCl₄ to save K[Pt(NH₃)Cl₃] which is very expensive and see if the created synthesis cis-Pt(NH₃)Cl₂-[benzothiazole] is effective on cancer cells.

This past month there have been diverse techniques I have learned in the investigation. In my last synthesis I learned to use infrared as far as I can say it was a great experience because it has been explained to me in such an easy way and I have the lucky of do it twice to not forget how it is done. Before, in my chemistry courses, I had studied what centrifuged was but I never put it into practice until this past month. In addition to other filtering techniques this month my mentor taught me another different way of filtrate. I use a needle with Acrodisc Nylon Plastic to remove impurities found in the synthesis. These techniques refined my results in this investigation. The best part is that in the future I will have the advantage of knowing these methods to perfect my skills in the laboratories.