Session IIB

Monday, May 16th

Session IIB


Towards the Synthesis of Fluorescent Sensors for Fe(II)

Akanksha Patel and Janet R. Morrow

University at Buffalo, Department of Chemistry

Iron is the most abundant transition metal found in the body. The accessibility of different oxidation states including Fe(II), Fe(III) and Fe(IV) makes iron a useful metal ion for the active sites of metalloenzymes. Consequently, iron is critical to the function of several biological enzymatic processes. Dyshomeostasis of cellular iron concentration in the brain has been found in a variety of neurodegenerative diseases including Alzheimer’s, Parkinson’s, Huntington’s and multiple Sclerosis. Whether abnormal iron levels are a cause or an effect of the onset of the disease remains unclear. Current methods to analyze Fe(II) trafficking in cells are underdeveloped. Fluorescence probes provide a means to investigate these pathways. Our approach towards this problem is to develop a fluorescence probe for Fe(II) that produces more intense fluorescence emission as the metal ion binds (“turn-on”). The design consists of a binding moiety and a sensing moiety. The binding moiety consists of macrocyclic ligands which can be functionalized to selectively bind to Fe(II) in the presence of other biologically relevant ions. The sensing moiety consists of a fluorophore which emits in visible region. The binding moiety and sensing moiety are connected via an aryl linker, which is critical towards the function of a turn on fluorescence probe. Preliminary studies with various biologically relevant metal ions shows fluorescence quenching in the case of Zn(II) and Cu(I) binding while an increase in fluorescence intensity was observed for Fe(II). These results suggest turn on behavior with respect to Fe(II) and thus shows promise towards the development of a useful fluorescence probe.



Heavy Chalcogen Containing Dyes for use in Dye-Sensitized Solar Cells

Kellie Davies, Michelle K. Linder, Jacqueline E. Hill, Justin N. Nasca, and Michael R. Detty

University at Buffalo, Department of Chemistry

The exploration of renewable energy sources has grown in interest due to the projected increase in global demand in the coming years. One such renewable energy source that could supply this demand is solar energy. The use of dye-sensitized solar cells to harvest solar energy, and the optimization of the dyes has been widely researched. The synthesis of several new heavy chalcogen containing dyes for the use in dye-sensitized solar cells will be described.



Synthesis and Biological Effects of Novel Biocompatible Agents for Boron Neutron Capture Therapy

Tianyu He, Sridar Chittur, and Rabi Musah

University at Albany, Department of Chemistry

Malignant brain tumors, which afflict ~250,000 people annually, are some of the most aggressive and hard-to-treat cancers. These tumors can be difficult to eliminate not only because of their rapid growth, but also because their location may make them inoperable. As a consequence, the development of effective treatments remains a high priority. Boron neutron capture therapy (BNCT) is a non-invasive potential treatment for locally invasive malignant brain tumors. It involves the use of drugs that contain the non-radioactive isotope boron-10 (10B) which has a high propensity to capture slow neutrons. Irradiation of the site to which 10B has been introduced results in the emission of high energy particles that kill the cancer cells. One approach to the design of biocompatible 10B-containing agents that might have therapeutic efficacy is to incorporate 10B into scaffolds found in nature, for example, amino acids, in order to introduce boron into molecules that are likely to be taken into the cells. Towards the goal of installing a boron-rich moiety into a biocompatible framework, we synthesized boron containing amino acids, and we report here on their effects in the immortalized malignant glioma cell line U87.



Neutral Lipids Accumulate During Replicative Senescence in Fibroblasts

Darleny Lizardo and G. Ekin Atilla-Gokcumen

University at Buffalo, Department of Chemistry

Cellular senescence is a state of permanent cell-cycle arrest that occurs following an extended period of proliferation in culture or in response to stress. Over the last couple of decades several studies have suggested that the senescence response evolved as a fail-safe mechanism to protect cells from cancer. Additionally, senescent cells have been shown to accumulate with age in human tissues suggesting that senescence may contribute to organismal aging. Upon entering the senescent state, cells undergo dramatic morphological and metabolic changes as well as changes in gene expression and protein processing. The molecular mechanisms underlying senescence have been heavily studied yet we still have a poor understanding of the role that lipids play in cellular senescence. In this study, the lipid profiles of proliferating and replicative senescent fibroblast cells were investigated using liquid chromatography–mass spectrometry. The comparative analysis of lipid profiles of senescent vs. proliferating cells allowed us to identify lipids that change during replicative senescence. Our findings show that there is a specific accumulation of triacylglycerols, a glycerolipid, in senescent fibroblasts. Our current efforts are toward elucidation of biochemical mechanisms that are responsible for these changes. Future work will focus on studying the functional involvement of the identified triacylglycerols. Gaining a better understanding of the causes and consequences of senescence may provide novel insights into how cells react to stress.