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The structural and energetic features of the attractive intramolecular through-space S-X interaction [X being oxygen (O) or sulfur (S)] of thioester containing 3-isothiazolidinone 1-oxide heterocycles are described. Density functional theoretical and semiempirical calculations are used to explain the previous X-ray data on 3-isothiazolidinone 1-oxides 5 and 6 [Kanda, Y., Ashizawa, T. , Kakita, S., Takahashi, Y., Kono, M., Yoshida, M., Saitoh, Y., and Okabe, M. (1999) J. Med. Chem. 42, 1330-1332] and implicate a mechanism where the adjacent thioester participates in an apical-directed stabilization of the sulfur heterocycle. A key factor that distinguishes the S-O interaction from the S-S interaction is the stronger through-space interaction of the former, which is a consequence of the greater electronegativity of apical O compared to apical S. Reaction field theory reveals that the conversion of the S-O interaction to the S-S interaction is more facile compared to gas phase computations, which suggest a reduced importance of the 1,5-S-X interactions in solution. The conversion of the S-O interaction to the S-S interaction gives an isothiazolidinone oxide that places the reacting sulfurs in proximity with an orientation presumably suitable for bond formation and access to the dithiolanone oxide surface. Factors that influence the through-space S-X interactions may represent important issues in identifying target 3-isothiazolidinone 1-oxide prodrugs capable of rearranging to 1,2-dithiolan-3-one 1-oxide drugs.

IntroductionUltrasound is a widely available but underutilized diagnostic tool. Ultrasound allows for real time evaluation and diagnosis of commonly encountered clinical problems, as well as treatment of patients at their bedside. Our goal was to evaluate the comfort level of medical students, housestaff and attending physicians in using ultrasound to diagnose and evaluate three common findings. MethodsA prospective cross-sectional study was performed. An anonymous survey was handed out to 29 attending physicians including subspecialists such as emergency room physicians, cardiologists, pulmonary critical care physicians and general surgeons, 60 medical residents and fellows and 15 medical students. They were asked to rate their level of comfort, from 1 to 5, using ultrasound to diagnose the 3 findings of pleural effusions, pneumothorax and B-lines which are seen in pulmonary edema. Findings 55% of attending physicians, 15% of housestaff and 0% of medical students felt comfortable using ultrasound in diagnosing pleural effusions. 13.7% of attending physicians, 8.3% of housestaff and 0% of medical students were comfortable with B-lines. 10.3% of attending physicians, 3.3% of housestaff and 0% of medical students felt comfortable in diagnosing a pneumothorax with ultrasound. Discussion Currently, ultrasound is not commonly performed or taught in medical residency programs. The most striking finding was that very few of the housestaff and none of the medical students surveyed were comfortable using ultrasound. Given the ease and availability of ultrasound, it may be beneficial to develop additional training modules early in medical school and in residency programs.

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