AM1 study of proton-transfer reactions of barbituric acid

Kakkar, Rita; Katoch, Vandana

doi:10.1002/(sici)1097-461x(1999)74:3<327::aid-qua5>3.0.co;2-o

Cited by 9 publications

(6 citation statements)

References 13 publications

(7 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Molecular modeling using MOPAC-type calculations show that these two protonated cyclic structures represent local minimum-energy conformations, implying considerable stabilization. MOPAC calculations have been used by many investigators to probe the stabilities of both the intra- and intermolecular structures of compounds and molecular assemblies; only a few references are provided here. − Stabilization due to hydrogen bonding effectively raises the activation energy ( E a2 ), necessary for nucleophilic attack by the monomer reaction to proceed to give the tertiary oxonium ion, and this effectively retards the formation of polymer. Factors that decrease the stabilization of the protonated species also decrease the activation energy barrier, E a2 .…”

Section: Resultsmentioning

confidence: 99%

Investigation of the Reactivity of Epoxide Monomers in Photoinitiated Cationic Polymerization

2005

View full text Add to dashboard Cite

An investigation of the photoinitiated cationic ring-opening polymerizations of various epoxy monomers was conducted using real-time infrared spectroscopy and optical pyrometry. Several types of behavior were observed and interpreted on the basis of the relative stabilities of the secondary and tertiary oxonium ion intermediates that are generated during the ring-opening polymerization of these monomers. Based on the mechanistic interpretations proposed, attempts were made to accelerate the photopolymerizations of epoxy monomers that undergo overall slow reaction as a result of the presence of an induction period. Three general methods were effective for the acceleration of the photopolymerizations of these and other epoxy monomers: (1) carrying out the photopolymerizations at higher temperatures, (2) copolymerization with more reactive monomers, and (3) the use of free radical photoinitiators.

show abstract

Section: Resultsmentioning

confidence: 99%

Investigation of the Reactivity of Epoxide Monomers in Photoinitiated Cationic Polymerization

2005

View full text Add to dashboard Cite

show abstract

“…61 Incorporation of water molecules has been found to lower the energy barrier for proton transfer, which enables this conversion to occur upon hydration. 62…”

Section: Crystal Growth and Designmentioning

confidence: 99%

Two Faces of Ciprofloxacin: Investigation of Proton Transfer in Solid State Transformations

Mesallati

Mugheirbi

Tajber

2016

Crystal Growth & Design

View full text Add to dashboard Cite

Ciprofloxacin (CIP) can exist in two different forms: the zwitterion and the unionized form. While the crystal structure of each has been described independently, the ability of CIP to transform from one to the other in the solid state has not been described. The crystal structures of unionized and zwitterionic CIP were therefore compared using computational methods, including their packing arrangement, hydrogen bonding, packing energy, intermolecular potentials and HOMO/LUMO energy gap. The pure amorphous form of CIP has also never been prepared or studied. Ball milling, cryomilling and spray drying were used in this study to prepare partially and fully amorphous CIP for the first time. The physical characteristics were examined by PXRD, FTIR and DSC. CIP proved to be very difficult to amorphize, and only spray drying in pure water resulted in a fully amorphous product. It was discovered that while most processing methods resulted in the more stable zwitterionic form of the drug, spray drying in an ethanol/water mixture produced the unionized form. The zwitterion was found to convert to the unionized form upon heating to its melting point, whereas the reverse transformation occurred when unionized CIP was exposed to high humidity. This study thus provides insight into the proton transfer which can occur in a zwitterionic drug in the solid state, and the resultant changes to its crystal structure. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 3 Abstract Ciprofloxacin (CIP) can exist in two different forms: the zwitterion and the unionized form.While the crystal structure of each has been described independently, the ability of CIP to transform from one to the other in the solid state has not been described. The crystal structures of unionized and zwitterionic CIP were therefore compared using computational methods, including their packing arrangement, hydrogen bonding, packing energy, intermolecular potentials and HOMO/LUMO energy gap. The pure amorphous form of this drug has also never been prepared or studied. Ball milling, cryomilling and spray drying were used in this study to prepare partially and fully amorphous CIP for the first time. The physical characteristics, and in particular ionization state, of these samples were examined by PXRD, FTIR and DSC. Analysis of the crystal packing of unionized and zwitterionic CIP revealed that the presence of ionic interactions between the charged groups of the latter results in a denser and more stable crystal lattice. A greater HOMO/LUMO energy gap was also calculated for this sample, confirming its lower reactivity. CIP proved to be very difficult to amo...

show abstract

“…In isolated BA, the tri-keto form (henceforth referred to as the keto form or keto tautomer, Figure a) is the most stable tautomer and the enol form (Figure b) is the second most stable tautomer based on several quantum chemical studies. ,− The most recent of these estimates the keto form to be about 11.6 kcal/mol more stable than the enol form . On the other hand, in the solid state, the enol form of BA has been found to be more stable than the keto form. , BA spontaneously converts from the keto to the enol form in the solid state upon prolonged storage .…”

Section: Introductionmentioning

confidence: 99%

Water-Controlled Keto–Enol Tautomerization of a Prebiotic Nucleobase

Datar

Paithankar²,

Deb

et al. 2022

J. Phys. Chem. B

View full text Add to dashboard Cite

Barbituric acid is believed to be a proto-RNA nucleobase that was used for biological information transfer on prebiotic earth before DNA and RNA in their present forms evolved. Nucleobases have various tautomeric forms and the relative stability of these forms is critical to their biological function. It has been shown that barbituric acid has a tri-keto form in the gas phase and an enol form in the solid state. However, its dominant tautomeric form in aqueous medium that is most relevant for biology has been investigated only to a limited extent and the findings are inconclusive. We have used multiple approaches, namely, molecular dynamics, quantum chemistry, NMR, and IR spectroscopy to determine the most stable tautomer of barbituric acid in solution. We find a delicate balance in the stability of the two tautomers, tri-keto and enol, which is tipped toward the enol as the extent of solvation by water increases.

show abstract

AM1 study of proton-transfer reactions of barbituric acid

Cited by 9 publications

References 13 publications

Investigation of the Reactivity of Epoxide Monomers in Photoinitiated Cationic Polymerization

Investigation of the Reactivity of Epoxide Monomers in Photoinitiated Cationic Polymerization

Two Faces of Ciprofloxacin: Investigation of Proton Transfer in Solid State Transformations

Water-Controlled Keto–Enol Tautomerization of a Prebiotic Nucleobase

Contact Info

Product

Resources

About