Jelena M. Mirković

Spectroscopic and quantum mechanical investigation of N,N′-bisarylmalonamides: solvent and structural effects

AbstractThe UV absorption spectra of ten N,N′-bisarylmalonamides have been recorded in the range 200–400xa0nm in a set of selected solvents. The solute–solvent interactions have been analyzed on the basis of the linear solvation energy relationship (LSER) concept proposed by Kamlet and Taft. The effects of substituents on the absorption spectra have been interpreted by correlating absorption frequencies with Hammett substituent constants. Furthermore, the experimental findings have been interpreted using the DFT CAM-B3LYP/6–311+G(d,p) method. Electronic energies have been calculated using the same method in combination with the implicit solvation model (conductor-like polarizable continuum model, CPCM) as well as with the explicit addition of two molecules of solvent.n Graphical AbstractRelationship between vmax and σp+ for the investigated N,N-bisarylmalonamides along with the optimized geometries for N,N-bisphenylmalonamide (4) with intramolecular H-bond (I), with intermolecular bonds with two explicit ethanol (II) and DMSO (III) molecules

Properties and synthesis of milrinone

Milrinone, 1,6-dihydro-2-methyl-6-oxo-[3,4’-bipyridine]-5-carbonitrile, is a n positive inotropic cardiotonic agent with vasodilator properties that acts as n selective phosphodiesterase 3 inhibitor in cardiac and vascular smooth n muscle. Trade names of milrinone are Primacor, Corotrop, Corotrope, and n Milrila. Milrinone, an amrinone derivative, is 20 to 50 times more active n than amrinone and possesses reduced propensity to side effects. The use of n milrinone has created controversy in the medical as the result of increased n mortality rate among patients that received high amounts of milrinone in oral n form. Reaserch show that it can be benifitial for patients with severe n congestive heart failure when used as short-time intravenous therapy. n Milrinone properties, stability, as well as mechanism of action and synthesis n under laboratory and industry conditions have been described in this paper. n For industrial purposes milrinone is synthesized by condensation of n cyanoacetamide with 4-(dimethylamino)-3-(4-pyridinyl)-3-buten-2-one and n 4-ethoxy-3-(4-pyridinyl)-3-buten-2-one in presence of a base, or by the n reaction of 1-(4-pyridinyl)- 2-propanone with ethoxymethylenmalononitrile or n 4-alkoxy-3-(4-pyridinyl)-3-buten-2-one with malononitrile without the use of n external base. The starting compound for these syntheses is 4-picoline. n Alternative synthesis of milrinone starts from n 2-methyl-3-(4-pyridylidiene)-1,1,5-tricyano-1,4-pentadiene-5-carboxamide and n 2-methyl-6-oxo-1,6-dihydro-3,4’-bipyridine-5-carboxamide. Lastly, methods for n milrinone synthesis in laboratory, injection preparation and purification n have been summarized.

Computational and spectroscopic data correlation study of N,N'-bisarylmalonamides (Part II)

To complement a previous UV study, we present a quantitative evaluation of substituent effects on spectroscopic data (1H and 13C NMR chemical shifts as well as FT-IR absorption frequency) applied to N,N-bisarylmalonamides, using simple and extended Hammett equations as well as the Swain-Lupton equation. Furthermore, the DFT CAM-B3LYP/6–311+G(d,p) method was applied to study the impact of different solvents on the geometry of the molecules and their spectral data. Additionally, experimental data are correlated with theoretical results; excellent linear dependence was obtained. The overall results presented in this paper show that N,N-bisarylmalonamides are prominent candidates for model molecules.