Synthesis of novel technetium-99m tricarbonyl-HBED-CC complexes and structural prediction in solution by density functional theory calculation

HBED-CC ( N,N' -bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylene diamine- N,N' -diacetic acid, L 1 ) is a common bifunctional chelating agent in preparation of 68 Ga-radiopharmaceuticals. Due to its high stability constant for the Ga 3+ complex (logK GaL = 38.5) and its acyclic structure, it is well known for a rapid and efficient radiolabelling at ambient temperature with Gallium-68 and its high in vivo stability. [ 99m Tc][Tc(CO) 3 (H 2 O) 3 ] + is an excellent precursor for radiolabelling of biomolecules. The aim of this study was to develop a novel preparation method of 99m Tc-HBED-CC complexes. In this study, HBED-CC-NI (2,2'-(ethane-1,2-diylbis((2-hydroxy-5-(3-((2-(2-nitro-1H-imidazol-1-yl)ethyl)amino)-3-oxopropyl)benzyl)-azanediyl))-diacetic acid, L 2 ), a derivative of HBED-CC, was designed and synthesized. Both L 1 and L 2 were radiolabelled by [ 99m Tc][Tc(CO) 3 (H 2 O) 3 ] + successfully for the first time. In order to explore the coordination mode of metal and chelates, non-radioactive Re(CO) 3 L 1 and Re(CO) 3 L 2 were synthesized and characterized spectroscopically. Tc(CO) 3 L 1 and Tc(CO) 3 L 2 in solution were calculated by density functional theory and were analysed with radio-HPLC chromatograms. It showed that [ 99m Tc]Tc(CO) 3 L 2 forms two stable diastereomers in solution, which is similar to those of [ 68 Ga]Ga-HBED-CC complexes. Natural bond orbital analysis through the natural population charges revealed a charge transfer between [ 99m Tc][Tc(CO) 3 ] + and L 1 or L 2 . The experimental results showed that tricarbonyl technetium might form stable complex with HBED-CC derivatives, which is useful for the future application of using HBED-CC as a bifunctional chelating agent in developing new 99m Tc-radiopharmaceuticals as diagnostic imaging agents.

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Research the sulfonation mechanism of urea in oleum by density functional theory calculation

Butlerov Communications ◽

10.37952/roi-jbc-01/19-59-8-32 ◽

2019 ◽

Vol 59 (8) ◽

pp. 32-39

Author(s):

Andrey A. Degtyarev ◽

◽

Alexandra V. Trishina ◽

Keyword(s):

Density Functional Theory ◽

Density Functional ◽

Activation Barrier ◽

Density Functional Theory Calculation ◽

Sulfamic Acid ◽

Isocyanic Acid ◽

Stable Complex ◽

Carbamic Acid ◽

Functional Theory ◽

Theory Calculation

The work investigates the sulfonation mechanism of urea in oleum, which is used in the synthesis of sulfamic acid. In addition to sulfamic acid, carbon dioxide is also released in the process. The method of density functional theory was used to model the sulfonation reaction using cation HSO3+ as a true sulfonating agent. All elementary acts, intermediates, and transition states of the reaction are determined. Six possible complexes of urea and cation HSO3+ are identified, of which two are reactive, formed through the bonding of the nitrogen atom of urea and sulfur of the HSO3+. The most stable complex is formed through the bonding of the oxygen atom of urea and sulfur of the HSO3+, from the reactive complexes it is separated by an activation barrier of 149.86 kJ/mol, so its formation inactivates the starting reagents and their return to a reactive state is possible only through interaction with negatively charged particles. The activation energies and thermal effects of the stages are calculated. The first stable intermediate of the process is isocyanic acid. Subsequently, isocyanic acid reacts with sulfuric by two mechanisms: the formation of urethane-like structures of NH2COOSO3H or carbamic acid. The second mechanism is preferred since it requires much milder conditions. Using the continuum models D-PCM and COSMO, the influence of the solvent on the reaction mechanism was studied. As a solvent, 100% sulfuric acid was taken. The maximum activation energy of elementary stages according to the first mechanism was: 167.37 (COSMO) kJ/mol, 169.77 (D-PCM), without solvent 180.38 kJ/mol. By the second mechanism: 57.38 (COSMO) kJ/mol, 59.91 (D-PCM), without solvent 91.15 kJ/mol. The number of elementary acts is 6 for the first mechanism and 7 for the second.

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