The Utilization of Alternative Synthetic Methods for Further Optimization of Cyanine Dyes and their Potential Use in Imaging and Photodynamic Therapy

The work presented in this thesis aims utilizes the versatility of cyanine dyes. Although large libraries have generated for these compounds, their remains an unmet need for alternative synthetic procedures that both optimizes and allows the dyes to be tailored for the desired use. The cyanine dye scaffold contains many points of modification but the central carbon remains a point that requires further research. In addition, among the heterocyclic compound that can be used in the synthesis of cyanine dyes, the quinoline heterocycle offer interesting optical variations to the dyes and can be utilized in the applications that do not require highly fluorescent compounds. The dyes presented showcase a superior synthetic procedure, and incorporate the quinoline heterocycle in novel compounds

The Benefits of Peer-Lead Mock Focused Exam Workshops

Context: Mock examinations are commonplace in many academic settings and are offered as a study aid to students with the hope of lowering stress levels and increasing their preparedness for the actual exam. In contrast, mock exams are rarely offered by faculty in clinical training due to their expense and administrative burden (1). Students taking objective structured clinical examinations, (OSCEs), have been proven to benefit from participating in mock exams (2). However, this is something that has not been explored in the context of the Focused Exam Workshop (FEW). While OSCEs focus solely on biomechanical skills, the FEW allows students to choose which physical exams are important for gathering information pertinent to creating a diagnosis and writing a SOAP note. In this study, we assess the efficacy of providing first year medical students with a mock exam prior to taking their FEW. This will stress the importance of implementing peer-organized mock examinations. Objective: Our study objective is to draw correlations between mock Focused Exam Workshop participation and overall performance on the course examination including final score, student stress levels, and biomechanical performance. This study will create a fundamental basis for understanding the effectiveness of participating in mock exams as preparation for all physical and clinically based skill examinations. Methods: The students were offered a SOAP note workshop and provided with complete exams specific to PCOM-GA curriculum as preparatory work prior to testing. Mock exams were then performed virtually with second year students acting as standardized patients (SP) with prepared case presentations. Thirty first year students acting as the doctor were asked to join the virtual rooms at different times and then perform a History and Physical with their SP focusing around a specific chief complaint that the students were unaware of before beginning the exam. Instructions were given on how the mock exam process will be conducted but no other hints were given to students regarding the context of the exam. Following the history and physical exam, the students were asked to create a SOAP note within the 9 minute limit offered by the COMLEX Level 2 PE exam (3). These SOAP notes were graded based on course description and COMLEX Level - 2 PE guideline by the student’s respective SP before the data was compiled. We also asked students to provide us with feedback through a Google Form that was sent out after the actual FEW was completed, so that they could provide us with extra information regarding their state of mind and chief complaint preferences among other things. All of this data was compiled and analyzed before being compared to student’s actual FEW scores which were provided to us without any identifying information, as to preserve student anonymity. IRB approval was obtained through the committee at the Philadelphia College of Osteopathic Medicine Georgia Campus. Results & Conclusions: Results are pending further stud

Synthesis and Optical Properties of Near-Infrared meso-Phenyl-Substituted Symmetric Heptamethine Cyanine Dyes

Heptamethine cyanine dyes are a class of near infrared fluorescence (NIRF) probes of great interest in bioanalytical and imaging applications due to their modifiability, allowing them to be tailored for particular applications. Generally, modifications at the meso-position of these dyes are achieved through Suzuki-Miyaura C-C coupling and SRN1 nucleophilic substitution of the chlorine atom at the meso-position of the dye. Herein, a series of 15 meso phenyl-substituted heptamethine cyanines was synthesized utilizing a modified dianil linker. Their optical properties, including molar absorptivity, fluorescence, Stokes shift, and quantum yield were measured. The HSA binding affinities of two representative compounds were measured and compared to that of a series of trimethine cyanines previously synthesized by our lab. The results indicate that the binding of these compounds to HSA is not only dependent on hydrophobicity, but may also be dependent on steric interferences in the binding site and structural dynamics of the NIRF compounds

Small Molecule Optoacoustic Contrast Agents: An Unexplored Avenue for Enhancing In Vivo Imaging

Almost every variety of medical imaging technique relies heavily on exogenous contrast agents to generate high-resolution images of biological structures. Organic small molecule contrast agents, in particular, are well suited for biomedical imaging applications due to their favorable biocompatibility and amenability to structural modification. PET/SPECT, MRI, and fluorescence imaging all have a large host of small molecule contrast agents developed for them, and there exists an academic understanding of how these compounds can be developed. Optoacoustic imaging is a relatively newer imaging technique and, as such, lacks well-established small molecule contrast agents; many of the contrast agents used are the same ones which have found use in fluorescence imaging applications. Many commonly-used fluorescent dyes have found successful application in optoacoustic imaging, but others generate no detectable signal. Moreover, the structural features that either enable a molecule to generate a detectable optoacoustic signal or prevent it from doing so are poorly understood, so design of new contrast agents lacks direction. This review aims to compile the small molecule optoacoustic contrast agents that have been successfully employed in the literature to bridge the information gap between molecular design and optoacoustic signal generation. The information contained within will help to provide direction for the future synthesis of optoacoustic contrast agents