Base pairs with 5-chloroorotic acid and comparison with the natural nucleobase. Structural and spectroscopic study, and three suggested antiviral modified nucleosides.

A structural and spectroscopic study of 5-chloroorotic acid (5-ClOA) biomolecule was carried out by IR and FT-Raman and the results obtained were compared to those achieved in 5-fluoroorotic acid and 5-aminoorotic acid compounds. The structures of all possible tautomeric forms were determined using DFT and MP2 methods. To know the tautomer form present in the solid state, the crystal unit cell was optimized through dimer and tetramer forms in several tautomeric forms. The keto form was confirmed through an accurate assignment of all the bands. For this purpose, an additional improvement in the theoretical spectra was carried out using linear scaling equations (LSE) and polynomic equations (PSE) deduced from uracil molecule. Base pairs with uracil, thymine and cytosine nucleobases were optimized and compared to the natural Watson-Crick (WC) pairs. The counterpoise (CP) corrected interaction energies of the base pairs were also calculated. Three nucleosides were optimized based on 5-ClOA as nucleobase, and their corresponding WC pairs with adenosine. These modified nucleosides were inserted in DNA:DNA and RNA:RNA microhelices, which were optimized. The position of the -COOH group in the uracil ring of these microhelices interrupts the DNA/RNA helix formation. Because of the special characteristic of these molecules they can be used as antiviral drugs.Communicated by Ramaswamy H. Sarma.

Base pairs with 4-amino-3-nitrobenzonitrile: comparison with the natural WC pairs. Dimer and tetramer forms, Infrared and Raman spectra, and several proposed antiviral modified nucleosides.

Base pairs of 4-amino-3-nitrobenzonitrile (4A-3NBN) molecule with uracil, thymine and cytosine nucleobases were optimized and compared to natural Watson-Crick (WC) pairs. The slightly greater flexibility of the -NO2 group of 4A-3NBN than the N3-H group of the natural nucleobases together with a noticeable higher dipole moment of its pairs can facilitate disruption of the DNA/RNA helix formation. Several new mutagenic modified nucleosides with 4A-3NBN and 3-amino-2-nitrobenzonitrile (3A-2NBN) were proposed as antiviral prodrugs and their base pairs optimized. The special characteristics of these prodrugs appear appropriated for their clinical use. The counterpoise (CP) corrected interaction energies of the base pairs were calculated and compared to the natural ones. The M06-2X DFT method was used for this purpose. The molecular structure of 4A-3NBN was analyzed in detail and the crystal unit cell was simulated by a tetramer form and eight dimer forms. The performance of the B3LYP, X3LYP and M06-2X methods was tested on the vibrational wavenumbers in the monomer, dimer and tetramer forms of 4A-3NBN. The observed IR and Raman bands were assigned according to the optimum dimer II form determined by B3LYP and by the tetramer form calculated by M06-2X, which is the expected unit cell that forms the crystal net. The two best scaling procedures were used.Communicated by Ramaswamy H. Sarma.

FT-IR, FT-Raman spectra and other molecular properties of 2,4- dichlorobenzonitrile: a interpretation by a DFT study.

FT-IR and FT-Raman spectra of 2,4-dichlorobenzonitrile at room temperature have been recorded in the regions 200-3500cm(-)(1) and 0-3400cm(-)(1), respectively. The observed vibrational bands were analyzed and assigned to different normal modes of the molecule according to the Wilson's notation. Density functional calculations were performed to support our frequency assignments. Specific scale equations deduced from the benzene molecule were employed to improve the calculated values. For the majority of the normal modes, the deviations between the corresponding experimental and scaled theoretical wavenumbers are located in the expected range. A correct characterization of each normal mode is of vital importance in the assignment of the observed bands, and the same has been successfully done by the aid of Potential Energy Distributions (PEDs) calculated separately for each normal mode of 2,4-dichlorobenzonitrile. The molecular structure was optimized and several thermodynamic parameters were determined. HOMO and LUMO orbital energy analysis were carried out.

Use and limitations of immediate postprocedural intracoronary Doppler blood flow measurements for predicting late result after coronary balloon angioplasty. Results of a pilot study.

BACKGROUND AND AIMS: Physiologic measurement of myocardial perfusion in the immediate postangioplasty period may complement the angiographic assessment of the outcome of the procedure and improve our ability to identify patients at increased risk for a suboptimal late result. Immediate in-lab identification of patients at risk for late coronary restenosis would allow the interventionalist to implement alternate interventional and/or pharmacologic strategies aimed at improving the long-term outcome of angioplasty. The present single-center pilot study was undertaken to examine prospectively the value of intracoronary Doppler flow measurements immediately postangioplasty for predicting long-term patency of the dilated coronary artery. PATIENTS AND METHODS: Coronary average peak flow velocity (APV) at rest and during hyperemia (6-18 micrograms intracoronary adenosine) and coronary flow reserve in the distal coronary segment were measured in 24 consecutive patients 10-15 min after successful elective coronary angioplasty. Volume flow (Q) was calculated as APV/2 coronary cross-sectional area heart rate. Coronary arterial vessels and narrowings were measured by quantitative angiography using a geometric based method and automated edge detection. The present study reports the findings in the 16 patients undergoing conventional balloon angioplasty for whom hard endpoint angiographic data were available 4.9 +/- 1.5 months after angioplasty. RESULTS: A linear relation was present between angiographically measured minimal luminal dimension immediately postangioplasty and the late angiographic result of the procedure (r = 0.71, p = 0.0005). A greater acute gain during angioplasty was predictive of a larger luminal dimension at late angiographic follow-up (p = 0.006). There was no relation between the immediate postangioplasty Doppler flow measurements and the late angiographic result of the procedure. Late luminal dimension was not related to immediate postangioplasty basal or hyperemia APV, nor to immediate postangioplasty basal or hyperemic volume flow or to coronary flow reserve (all NS). CONCLUSIONS: In this single-center study, intracoronary blood flow and Doppler-derived coronary flow reserve immediately postpercutaneous transluminal coronary angioplasty were not predictive of long-term vessel patency or late coronary restenosis. The immediate angiographic result of angioplasty did correlate with the late result of the procedure.