Novel Photochemical Methodologies For Diversity Oriented Synthesis And Screening Of Combinatorial Libraries

The main goal of this project was to develop an efficient methodology allowing rapid access to structurally diverse scaffolds decorated with various functional groups. Initially, we discovered and subsequently developed an experimentally straightforward, high-yielding photoinduced conversion of readily accessible diverse starting materials into polycyclic aldehydes and their (hemi)acetals decorated by various pendants. The two step sequence, involving the Diels-Alder addition of heterocyclic chalcones and other benzoyl ethylenes to a variety of dienes, followed by the Paternò-Büchi reaction, was described as an alkene-carbonyl oxametathesis. This methodology offers a rapid increase in molecular complexity and diversity of the target scaffolds. To develop this novel methodology further and explore its generality, we directed our attention to the Diels-Alder adducts based on various chromones. We discovered that the Diels-Alder adducts of chromones are capable of photoinduced alkene-arene [2+2] cycloaddition producing different dienes, which can either dimerize or be introduced into a double-tandem [4π+2π]·[2π+2π]·[4π+2π]·[2π+2π] synthetic sequence, followed by an acid-catalyzed oxametathesis, leading to a rapid expansion of molecular complexity over a few experimentally simple steps. In view of the fact that oxametathesis previously was primarily observed in aromatic oxetanes, we decided to prepare model aliphatic oxetanes with a conformationally unconstrained or "flexible" methyl group based on the Diels-Alder adducts of cyclohexadiene or cyclopentadiene with methyl vinyl ketone. Upon addition of an acid, the expected oxametathesis occurred with results similar to those observed in the aromatic series proving the generality of this approach. Also we synthesized polycyclic oxetanes resulting from the Diels-Alder adducts of cyclic ketones. This not only gave us access to remarkably strained oxetane systems, but also the mechanism for their protolytic ring opening provided a great deal of insight to how the strain affects the reactivity. Additionally, we discovered that although the model Hetero-Diels-Alder adducts did not undergo [2+2] cycloaddition, both exo- and endo-Sulfa-Diels-Alder products, nonetheless, were photochemically active and various products with defined stereochemistry could be produced upon photolysis. In conclusion, we have developed an approach to the encoding and screening of solution phase libraries based on the photorelease of externally sensitized photolabile tags. The encoding tags can be released into solution only when a binding event occurs between the ligand and the receptor, equipped with an electron transfer sensitizer. The released tags are analyzed in solution revealing the identity of the lead ligand or narrowing the range of potential leads.

Psychosocial Distress Screening in a Community Cancer Center: An Exploratory Study of Distress Screening Across the Cancer Treatment Continuum

Purpose: The primary goal of this exploratory study is to demonstrate that distress screening across the course of cancer treatment is possible and provides valuable information about patient needs over time. Distress screening is aligned with guidelines from national accrediting organizations and may lead to improved health-related quality of life, satisfaction with medical care, and possibly survival.Methods: Medical, surgical, and radiation oncology patients completed a screening instrument before their appointments during a six-month period. Patients indicated their level of distress on four domains (practical, emotional, health and social concerns). De-identified data was collected, aggregated and descriptive statistics were analyzed.Results: Approximately 3000 screens were collected and 1500 cancer patients were screened. Of patients who indicated distress, 54% demonstrated a distress level of five or greater. Distress level eight was the most frequent level of distress indicated. The Cancer Dietitian was the most commonly requested healthcare team provider. The Health Concern domain was most frequently endorsed.Conclusion: NCCN, IOM and COC guidelines recommend distress screening in all cancer treatment centers, however implementation has proven difficult. This study adds to the literature about distress in cancer patients, demonstrates the feasibility of repeated distress screening and provides a model program demonstrating the implementation of repeated distress screening at a community cancer center. Findings highlight the importance of supportive oncology services due to the prevalence of high levels of distress. Findings demonstrate the importance of the Cancer Dietitian in supportive cancer care. Additionally, the research reveals a potential perceived stigma in seeking psychosocial oncology services.