Eight salt forms of sulfadiazine

Amanda Buist, Lynn Dennany, Alan Kennedy, Craig Manzie, Katherine McPhie, Brandon Walker

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Proton transfer to the sulfa drug sulfadiazine [systematic name: 4-amino-N-(pyrimidin-2-yl)benzenesulfonamide] gave eight salt forms. These are the monohydrate and methanol hemisolvate forms of the chloride (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium chloride monohydrate, C10H11N4O2S+·Cl−·H2O, (I), and 2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium chloride methanol hemisolvate, C10H11N4O2S+·Cl−·0.5CH3OH, (II)); a bromide monohydrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium bromide monohydrate, C10H11N4O2S+·Br−·H2O, (III)), which has a disordered water channel; a species containing the unusual tetraiodide dianion [bis(2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium) tetraiodide, 2C10H11N4O2S+·I42−, (IV)], where the [I4]2− ion is located at a crystallographic inversion centre; a tetrafluoroborate monohydrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium tetrafluoroborate monohydrate, C10H11N4O2S+·BF4−·H2O, (V)); a nitrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium nitrate, C10H11N4O2S+·NO3−, (VI)); an ethanesulfonate {4-[(pyrimidin-2-yl)sulfamoyl]anilinium ethanesulfonate, C10H11N4O2S+·C2H5SO3−, (VII)}; and a dihydrate of the 4-hydroxybenzenesulfonate {4-[(pyrimidin-2-yl)sulfamoyl]anilinium 4-hydroxybenzenesulfonate dihydrate, C10H11N4O2S+·HOC6H4SO3−·2H2O, (VIII)}. All these structures feature alternate layers of cations and of anions where any solvent is associated with the anion layers. The two sulfonate salts are protonated at the aniline N atom and the amide N atom of sulfadiazine, a tautomeric form of the sulfadiazine cation that has not been crystallographically described before. All the other salt forms are instead protonated at the aniline group and on one N atom of the pyrimidine ring. Whilst all eight species are based upon hydrogen-bonded centrosymetric dimers with graph set R22(8), the two sulfonate structures also differ in that these dimers do not link into one-dimensional chains of cations through NH3-to-SO2 hydrogen-bonding interactions, whilst the other six species do. The chloride methanol hemisolvate and the tetraiodide are isostructural and a packing analysis of the cation positions shows that the chloride monohydrate structure is also closely related to these.
LanguageEnglish
Pages900-907
Number of pages8
JournalActa Crystallographica Section C: Structural Chemistry
Volume70
Issue number9
DOIs
Publication statusPublished - Sep 2014

Fingerprint

Sulfadiazine
Cations
Chlorides
Salts
Positive ions
chlorides
salts
Methanol
Aniline
cations
Bromides
Dimers
Nitrates
Atoms
methyl alcohol
Anions
sulfonates
aniline
Negative ions
nitrates

Keywords

  • crystal structure
  • sulfa drugs
  • sulfadiazine
  • salt forms
  • tautomerism
  • pharmaceutical compounds
  • tetraiodide
  • active pharmaceutical ingredients

Cite this

Buist, Amanda ; Dennany, Lynn ; Kennedy, Alan ; Manzie, Craig ; McPhie, Katherine ; Walker, Brandon. / Eight salt forms of sulfadiazine. In: Acta Crystallographica Section C: Structural Chemistry. 2014 ; Vol. 70, No. 9. pp. 900-907.
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abstract = "Proton transfer to the sulfa drug sulfadiazine [systematic name: 4-amino-N-(pyrimidin-2-yl)benzenesulfonamide] gave eight salt forms. These are the monohydrate and methanol hemisolvate forms of the chloride (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium chloride monohydrate, C10H11N4O2S+·Cl−·H2O, (I), and 2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium chloride methanol hemisolvate, C10H11N4O2S+·Cl−·0.5CH3OH, (II)); a bromide monohydrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium bromide monohydrate, C10H11N4O2S+·Br−·H2O, (III)), which has a disordered water channel; a species containing the unusual tetraiodide dianion [bis(2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium) tetraiodide, 2C10H11N4O2S+·I42−, (IV)], where the [I4]2− ion is located at a crystallographic inversion centre; a tetrafluoroborate monohydrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium tetrafluoroborate monohydrate, C10H11N4O2S+·BF4−·H2O, (V)); a nitrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium nitrate, C10H11N4O2S+·NO3−, (VI)); an ethanesulfonate {4-[(pyrimidin-2-yl)sulfamoyl]anilinium ethanesulfonate, C10H11N4O2S+·C2H5SO3−, (VII)}; and a dihydrate of the 4-hydroxybenzenesulfonate {4-[(pyrimidin-2-yl)sulfamoyl]anilinium 4-hydroxybenzenesulfonate dihydrate, C10H11N4O2S+·HOC6H4SO3−·2H2O, (VIII)}. All these structures feature alternate layers of cations and of anions where any solvent is associated with the anion layers. The two sulfonate salts are protonated at the aniline N atom and the amide N atom of sulfadiazine, a tautomeric form of the sulfadiazine cation that has not been crystallographically described before. All the other salt forms are instead protonated at the aniline group and on one N atom of the pyrimidine ring. Whilst all eight species are based upon hydrogen-bonded centrosymetric dimers with graph set R22(8), the two sulfonate structures also differ in that these dimers do not link into one-dimensional chains of cations through NH3-to-SO2 hydrogen-bonding interactions, whilst the other six species do. The chloride methanol hemisolvate and the tetraiodide are isostructural and a packing analysis of the cation positions shows that the chloride monohydrate structure is also closely related to these.",
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Eight salt forms of sulfadiazine. / Buist, Amanda; Dennany, Lynn; Kennedy, Alan; Manzie, Craig; McPhie, Katherine; Walker, Brandon.

In: Acta Crystallographica Section C: Structural Chemistry, Vol. 70, No. 9, 09.2014, p. 900-907.

Research output: Contribution to journalArticle

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T1 - Eight salt forms of sulfadiazine

AU - Buist, Amanda

AU - Dennany, Lynn

AU - Kennedy, Alan

AU - Manzie, Craig

AU - McPhie, Katherine

AU - Walker, Brandon

PY - 2014/9

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N2 - Proton transfer to the sulfa drug sulfadiazine [systematic name: 4-amino-N-(pyrimidin-2-yl)benzenesulfonamide] gave eight salt forms. These are the monohydrate and methanol hemisolvate forms of the chloride (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium chloride monohydrate, C10H11N4O2S+·Cl−·H2O, (I), and 2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium chloride methanol hemisolvate, C10H11N4O2S+·Cl−·0.5CH3OH, (II)); a bromide monohydrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium bromide monohydrate, C10H11N4O2S+·Br−·H2O, (III)), which has a disordered water channel; a species containing the unusual tetraiodide dianion [bis(2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium) tetraiodide, 2C10H11N4O2S+·I42−, (IV)], where the [I4]2− ion is located at a crystallographic inversion centre; a tetrafluoroborate monohydrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium tetrafluoroborate monohydrate, C10H11N4O2S+·BF4−·H2O, (V)); a nitrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium nitrate, C10H11N4O2S+·NO3−, (VI)); an ethanesulfonate {4-[(pyrimidin-2-yl)sulfamoyl]anilinium ethanesulfonate, C10H11N4O2S+·C2H5SO3−, (VII)}; and a dihydrate of the 4-hydroxybenzenesulfonate {4-[(pyrimidin-2-yl)sulfamoyl]anilinium 4-hydroxybenzenesulfonate dihydrate, C10H11N4O2S+·HOC6H4SO3−·2H2O, (VIII)}. All these structures feature alternate layers of cations and of anions where any solvent is associated with the anion layers. The two sulfonate salts are protonated at the aniline N atom and the amide N atom of sulfadiazine, a tautomeric form of the sulfadiazine cation that has not been crystallographically described before. All the other salt forms are instead protonated at the aniline group and on one N atom of the pyrimidine ring. Whilst all eight species are based upon hydrogen-bonded centrosymetric dimers with graph set R22(8), the two sulfonate structures also differ in that these dimers do not link into one-dimensional chains of cations through NH3-to-SO2 hydrogen-bonding interactions, whilst the other six species do. The chloride methanol hemisolvate and the tetraiodide are isostructural and a packing analysis of the cation positions shows that the chloride monohydrate structure is also closely related to these.

AB - Proton transfer to the sulfa drug sulfadiazine [systematic name: 4-amino-N-(pyrimidin-2-yl)benzenesulfonamide] gave eight salt forms. These are the monohydrate and methanol hemisolvate forms of the chloride (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium chloride monohydrate, C10H11N4O2S+·Cl−·H2O, (I), and 2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium chloride methanol hemisolvate, C10H11N4O2S+·Cl−·0.5CH3OH, (II)); a bromide monohydrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium bromide monohydrate, C10H11N4O2S+·Br−·H2O, (III)), which has a disordered water channel; a species containing the unusual tetraiodide dianion [bis(2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium) tetraiodide, 2C10H11N4O2S+·I42−, (IV)], where the [I4]2− ion is located at a crystallographic inversion centre; a tetrafluoroborate monohydrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium tetrafluoroborate monohydrate, C10H11N4O2S+·BF4−·H2O, (V)); a nitrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium nitrate, C10H11N4O2S+·NO3−, (VI)); an ethanesulfonate {4-[(pyrimidin-2-yl)sulfamoyl]anilinium ethanesulfonate, C10H11N4O2S+·C2H5SO3−, (VII)}; and a dihydrate of the 4-hydroxybenzenesulfonate {4-[(pyrimidin-2-yl)sulfamoyl]anilinium 4-hydroxybenzenesulfonate dihydrate, C10H11N4O2S+·HOC6H4SO3−·2H2O, (VIII)}. All these structures feature alternate layers of cations and of anions where any solvent is associated with the anion layers. The two sulfonate salts are protonated at the aniline N atom and the amide N atom of sulfadiazine, a tautomeric form of the sulfadiazine cation that has not been crystallographically described before. All the other salt forms are instead protonated at the aniline group and on one N atom of the pyrimidine ring. Whilst all eight species are based upon hydrogen-bonded centrosymetric dimers with graph set R22(8), the two sulfonate structures also differ in that these dimers do not link into one-dimensional chains of cations through NH3-to-SO2 hydrogen-bonding interactions, whilst the other six species do. The chloride methanol hemisolvate and the tetraiodide are isostructural and a packing analysis of the cation positions shows that the chloride monohydrate structure is also closely related to these.

KW - crystal structure

KW - sulfa drugs

KW - sulfadiazine

KW - salt forms

KW - tautomerism

KW - pharmaceutical compounds

KW - tetraiodide

KW - active pharmaceutical ingredients

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JO - Acta Crystallographica Section C: Structural Chemistry

T2 - Acta Crystallographica Section C: Structural Chemistry

JF - Acta Crystallographica Section C: Structural Chemistry

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