Resonance Raman Spectroscopy of the Oxygenated Intermediates of Human CYP19A1 Implicates a Compound I Intermediate in the Final Lyase Step

CYP19A1, or aromatase, a cytochrome P450 responsible for estrogen biosynthesis in humans, is an important therapeutic target for the treatment of breast cancer. There is still controversy surrounding the identity of reaction intermediate that catalyzes carbon–carbon scission in this key enzyme. Probing the oxy-complexes of CYP19A1 poised for hydroxylase and lyase chemistries using resonance Raman spectroscopy and drawing a comparison with CYP17A1, we have found no significant difference in the frequencies or isotopic shifts for these two steps in CYP19A1. Our experiments implicate the involvement of Compound I in the terminal lyase step of CYP19A1 catalysis

Radiotracers for SPECT imaging: Current scenario and future prospects

Single photon emission computed tomography (SPECT) has been the cornerstone of nuclear medicine and today it is widely used to detect molecular changes in cardiovascular, neurological and oncological diseases. While SPECT has been available since the 1980s, advances in instrumentation hardware, software and the availability of new radiotracers that are creating a revival in SPECT imaging are reviewed in this paper. The biggest change in the last decade has been the fusion of CT with SPECT, which has improved attenuation correction and image quality. Advances in collimator design, replacement of sodium iodide crystals in the detectors with cadmium zinc telluride (CZT) detectors as well as advances in software and reconstruction algorithms have all helped to retain SPECT as a much needed and used technology. Today, a wide spectrum of radiotracers is available for use in cardiovascular, neurology and oncology applications. The development of several radiotracers for neurological disorders is briefly described in this review, including [ 123I]FP-CIT (DaTSCAN ™) available for Parkinson's disease. In cardiology, while technetium-99m labeled tetrofosmin and technetium-99m labeled sestamibi have been well known for myocardial perfusion imaging, we describe a recently completed multicenter clinical study on the use of [ 123I]mIBG (AdreView ™) for imaging in chronic heart failure patients. For oncology, while bone scanning has been prevalent, newer radiotracers that target cancer mechanisms are being developed. Technetium-99m labeled RGD peptides have been reported in the literature that can be used for imaging angiogenesis, while technetium-99m labeled duramycin has been used to image apoptosis. While PET/CT is considered to be the more advanced technology particularly for oncology applications, SPECT continues to be the modality of choice and the workhorse in many hospitals and nuclear medicine centers. The cost of SPECT instruments also makes them more attractive in developing countries where the cost of a scan is still prohibitive for many patients

ESR, raman and conductivity studies on fractionated poly(2-methoxyaniline-5-sulfonic acid)

Synthesis methods used to produce poly(2-methoxyaniline-5-sulfonic acid) (PMAS), a water soluble, self-doped conducting polymer, have been shown to form two distinctly different polymer fractions with molecular weights of approximately 2 kDa and 8 -10 kDa. The low molecular weight (LMWT) PMAS fraction is redox inactive and non-conducting while the high molecular weight (HMWT) PMAS is electro-active with electrical conductivities of 0.94 0.05 S cm-1. Previous investigations have illustrated the different photochemical and electrochemical properties of these fractions, but have not correlated these properties with the structural and electronic interactions that drive them. Incomplete purification of the PMAS mixture, typically via bag dialysis, has been shown to result in a mixture of approximately 50:50 HMWT:LMWT PMAS with electrical conductivity significantly lower at approximately 0.10 to 0.26 S cm-1. The difference between the electrical conductivities of these fractions has been investigated by the controlled addition of the non-conducting LMWT PMAS fraction into the HMWT PMAS composite film with the subsequent electronic properties investigated by solid-state ESR and Raman spectroscopies. These studies illustrate strong electronic intereactions of the insulating LMWT PMAS with the emeraldine salt HMWT PMAS to substantially alter the population of the electronic charge carriers in the conducting polymer. ESR studies on these mixtures, when compared to HMWT PMAS, exhibited a lower level of electron spin in the presence of LMWT PMAS indicative of the the formation of low spin bipolarons without a change the oxidation state of the conducting HMWT fraction