Sublimation Enthalpies of 5-Haloderivatives of 1,3-Dimethyluracil

Brunetti, Bruno; Irrera, Simona; Portalone, Gustavo

doi:10.1021/je500719p

Cited by 8 publications

(6 citation statements)

References 41 publications

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“…In this context, because of our long-term interest in the potential of pyrimidine nucleobases for crystal engineering strategies underpinned by multiple hydrogen bonds, − and our earlier experience with binary systems showing XB via alternative donors (i.e., halogen atom not polarized by fluorine), − we were interested to investigate the supramolecular architectures in biological systems, i.e., in cocrystals formed by haloderivatives of uracil coupled with amino-aromatic N -heterocycles, where the ability to distinguish between base pairing is offered by A → B proton-transfer reactions. Consequently, we focused our attention on a systematic XRD analysis of A–B cocrystals containing in different stoichiometric ratios uracil or 1-methyluracil derivatives with halide modification at the 5 position (coformer A), coupled with an amino-derivative of aromatic N -heterocycles (coformer B) (Scheme ).…”

Section: Introductionmentioning

confidence: 99%

Multifacial Recognition in Binary and Ternary Cocrystals from 5-Halouracil and Aminoazine Derivatives

Portalone

2018

Crystal Growth & Design

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A systematic analysis using single crystal X-ray diffraction was performed to explore the role exerted by potential intercomponent proton-transfer reactions in the supramolecular structures of A-B cocrystals formed by 5-haloderivatives of uracil (A) coupled with 2-aminoadenine simulants (aminoazines, B). Twelve new heterodimers were synthesized in different stoichiometry and cocrystallized by solvent co-grinding followed by solution crystallization. In the binary cocrystals, uracil or 1-methyluracil with halide modification at the 5 position (F, Cl, Br, I) were coupled with aminoaromatic N-heterocycles (melamine, 2,4,6-triaminopyrimidine, 2,6-diaminopyridine) as multivalent site for pyrimidine nucleobase recognition. The crystallographic analysis showed that, next to the expected neutral three-point hydrogen bonds (TPI), ionized TPI, favored by A → B proton transfer, can be used for WC multifacial recognition. Noteworthy, the formation of the charged TPI, which depends on the acid/base properties of the components, takes always place between the more acidic site of the 5halonucleobases (N3 atom) and the more basic site (imino N atom) of 2,4,6-triaminopyrimidine or 2,6diaminopyridine, and melamine recognition unit results to be insufficiently basic to accept a proton. The general ability of pyrimidine nucleobases to provide electron donating groups to halogen bonding has been confirmed in seven cocrystals containing the 5-chloro, 5-bromo or 5-iododerivatives coupled with melamine or 2,4,6-triaminopyrimidine. Considerations of the relative acidities of coformers A and of the relative basicities of coformers B allowed us to design and characterize by single-crystal X-ray diffraction the first ternary pyrimidine nucleobase-containing cocrystal based on the JANUS-WEDGE concept: the nucleobase-Janus-nucleobase (1:1:1) triad showing a 2,4,6-triamino pyrimidine molecule wedged via neutral and ionized TPI between the 5-fluorouracil/1-methyluracil pair in reverse WC fashion. ABSTRACTA systematic analysis using single crystal X-ray diffraction was performed to explore the role exerted by potential intercomponent proton-transfer reactions in the supramolecular structures of A-B cocrystals formed by 5-haloderivatives of uracil (A), coupled with 2-aminoadenine simulants (aminoazines, B). Twelve new heterodimers were synthesized in different stoichiometry and cocrystallized by solvent co-grinding followed by solution crystallization. In the binary cocrystals, uracil or 1-methyluracil with halide modification at the 5 position (F, Cl, Br, I) were coupled with amino-aromatic N-heterocycles (melamine, 2,4,6-triaminopyrimidine, 2,6-diaminopyridine) as multivalent site for pyrimidine nucleobase recognition. The crystallographic analysis showed that, next to the expected neutral three-point hydrogen bonds (TPI), ionized TPI, favored by A → B proton transfer, can be used for WC multifacial recognition. Noteworthy, the formation of the charged TPI, which depends on the acid/base properties of the components, takes always place between ...

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Section: Introductionmentioning

confidence: 99%

Multifacial Recognition in Binary and Ternary Cocrystals from 5-Halouracil and Aminoazine Derivatives

Portalone

2018

Crystal Growth & Design

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“…Sun et al have reported the fibril formation of 5-FU dilysine conjugates . The significant role of hydrogen bonding on the aggregation behavior of small organic molecules is reported in the literature. , On the contrary, N -methylation at the 1- and 3- positions of 5-FU makes 5-fluoro-1,3-dimethyluracil (5-FDMU), which lacks strong hydrogen-bond donors. , The stabilizing forces are weak CH···O hydrogen bonds and dipole-induced dipole interactions in 5-FDMU . In 2014, Majhi et al showed the effect of methylation on the self-assembly of 4-aminophthalimide, which indicates a prominent role of hydrogen bonding on the self-assembly of small molecules …”

Section: Introductionmentioning

confidence: 99%

“…20,21 On the contrary, N-methylation at the 1-and 3-positions of 5-FU makes 5-fluoro-1,3-dimethyluracil (5-FDMU), which lacks strong hydrogen-bond donors. 22,23 The stabilizing forces are weak CH•••O hydrogen bonds and dipole-induced dipole interactions in 5-FDMU. 22 In 2014, Majhi et al showed the effect of methylation on the self-assembly of 4-aminophthalimide, which indicates a prominent role of hydrogen bonding on the self-assembly of small molecules.…”

Section: Introductionmentioning

confidence: 99%

Unveiling the Self-Assembling Behavior of 5-Fluorouracil and its N,N′-Dimethyl Derivative: A Spectroscopic and Microscopic Approach

et al. 2017

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Under physiological conditions, 5-fluorouracil (5-FU), an anticancer drug, self-assembles into fibrils by strong hydrogen-bonding network, whereas its N,N'-dimethyl derivative, 5-fluoro-1,3-dimethyluracil (5-FDMU), does not make fibrils due to lack of strong hydrogen-bonding motif. In vitro, 5-FU self-assembly is sensitive to physicochemical conditions like the pH and ionic strength of the solution, which tune the strength of the noncovalent driving forces. Here we report a surprising finding that the buffer, which is necessary to control the pH and is typically considered to be inert, also significantly influences 5-FU self-assembly, which indicates an important role of counterions in the fibril formation. We have also monitored concentration- and time-dependent fibrillar growth of 5-FU. Again, fibril growth process is probed under dynamic conditions using microfluidic platform. The self-assembly of 5-FU compared with its N,N'-dimethyl derivative shows lower cytotoxicity to the cultured human erythroleukemic cells (K562 cells), which plausibly states the reason behind the greater effectiveness of 5-FU derivative drugs than 5-FU itself.

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“…In a continuation of a long-term interest in crystal engineering of DNA/RNA bases [12][13][14][15][16][17][18][19][20][21] and in systems exhibiting halogen bonding via alternative donors [8,11], this work focuses on the XBs exhibited by pyrimidine nucleobases carrying at the C6 position a halogen atom and at the C2 and the C4 positions two nucleophilic oxygen atoms. This investigation was then extended to the two new polymorphs obtained for 5-chloro and 5-bromouracil and their (1:1) cocrystal (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Site Selectivity of Halogen Oxygen Bonding in 5- and 6-Haloderivatives of Uracil

Portalone

2019

Crystals

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Seven 5-and 6-halogenated derivatives of uracil or 1-methyluracil (halogen = Cl, Br, I) were studied by single crystal X-ray diffraction. In contrast with pure 5-halouracils, where the presence of N-H…O and C-H…O hydrogen bonds prevents the formation of other intermolecular interactions, the general ability of pyrimidine nucleobases to provide electron donating groups to halogen bonding was confirmed in three crystals and cocrystals containing uracil with the halogen atom at the C6 position. In the latter compounds, among the two nucleophilic oxygen atoms in the C=O moiety, only the urea carbonyl oxygen O1 can act as halogen bond acceptor, being not saturated by conventional hydrogen bonds. The halogen bonds in pure 6-halouracils are all rather weak, as supported by Hirshfeld surface analysis. The strongest interaction was found in the structure of 6-iodouracil, which displayed the largest (13%) reduction of the sum of van der Waals (vdW) radii for the contact atoms. Despite this, halogen bonding plays a role in determining the crystal packing of 6-halouracils, acting alongside conventional hydrogen bonds.

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Sublimation Enthalpies of 5-Haloderivatives of 1,3-Dimethyluracil

Cited by 8 publications

References 41 publications

Multifacial Recognition in Binary and Ternary Cocrystals from 5-Halouracil and Aminoazine Derivatives

Multifacial Recognition in Binary and Ternary Cocrystals from 5-Halouracil and Aminoazine Derivatives

Unveiling the Self-Assembling Behavior of 5-Fluorouracil and its N,N′-Dimethyl Derivative: A Spectroscopic and Microscopic Approach

Site Selectivity of Halogen Oxygen Bonding in 5- and 6-Haloderivatives of Uracil

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