A study of the crystal and molecular structures of phenols with only intermolecular hydrogen bonding

Prout, Keith; Fail, J.; Jones, R. Morley; Warner, R. E.; Emmett, J. C.

doi:10.1039/p29880000265

Cited by 30 publications

(24 citation statements)

References 6 publications

(7 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The x-ray coordinates for propofol were utilized in this study [13]. Test compounds 2 and 5 were constructed from the propofol crystal structure by adding the appropriate atoms within the build edit mode of SYBYL (Tripos Inc.) This modified structure was energy-minimized with the Tripos force field [14], without solvent, using default bond distances and angles and neglecting electrostatics.…”

Section: Methodsmentioning

confidence: 99%

Comparative molecular field analysis and synthetic validation of a hydroxyamide-propofol binding and functional block of neuronal voltage-dependent sodium channels

Brown

Eidam

Paige

et al. 2009

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

Voltage gated sodium channels represent an important therapeutic target for a number of neurological disorders including epilepsy. Unfortunately, medicinal chemistry strategies for discovering new classes of antagonist for trans-membrane ion channels have been limited to mostly broad screening compound arrays. We have developed new sodium channel antagonist based on a propofol scaffold using the ligand based strategy of comparative molecular field analysis (CoMFA). The resulting CoMFA model was correlated and validated to provide insights into the design of new antagonists and to prioritize synthesis of these new structural analogues (compounds 4 and 5) that satisfied the steric and electrostatic model. Compounds 4 and 5 were evaluated for [3H]-batrachotoxinin-A-20-α-benzoate ([3H]-BTX-B) displacement yielding IC50's of 22 and 5.7 μM, respectively. We further examined the potency of these two compounds to inhibit neuronal sodium currents recorded from cultured hippocampal neurons. At a concentration of 50 μM, compounds 4 and 5 tonically inhibited sodium channels currents by 59 ± 7.8% (n=5) and 70 ± 7.5% (n=7) respectively. This clearly demonstrates that these compounds functionally antagonize native neuronal sodium channel currents. In summary, we have shown that CoMFA can be effectively used to discover new classes of sodium channel antagonists.

show abstract

Section: Methodsmentioning

confidence: 99%

Comparative molecular field analysis and synthetic validation of a hydroxyamide-propofol binding and functional block of neuronal voltage-dependent sodium channels

Brown

Eidam

Paige

et al. 2009

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…However, the space group, P2 1 /n, of the 3,5-dichloroBA crystal is different from that of AXBA, and the acid protons are ordered with the two clearly distinct carbon−oxygen interatomic lengths of R(CO) = 1.246 Å and R(C−O) = 1.286 Å at 173 K. 34 A proton-disordered phase was realized in 4-hydroxy-3,5-diiodoBA with the same space group, Pmna, and essentially the same lattice constants and molecular packing as in AIBA at room temperature. 30 With regard to the halogen bond, the bond lengths of the four-member iodine ring are short enough; 3.746 Å (0.95 times van der Waals diameter) and 4.008 Å (1.01 times van der Waals diameter) are close to those in the AIBA crystal. The hydroxy group at para position forms hydrogen bonds with two carboxylic-oxygen atoms equivalently like the amino group in AIBA.…”

Section: Resultsmentioning

confidence: 96%

Halogen Bond as Controlling the Crystal Structure of 4-Amino-3,5-Dihalogenobenzoic Acid and Its Effect on the Positional Ordering/Disordering of Acid Protons

Ueda

Oguni

Asaji

2014

Crystal Growth & Design

View full text Add to dashboard Cite

Crystal structures and thermal behaviors of 4-amino-3,5-dihalogenobenzoic acid (AXBA: X = Cl and I) were studied by single-crystal X-ray diffractometry and differential scanning calorimetry. It was found that all the crystal structures of AClBA and AIBA as well as ABrBA at room temperature belong to the same space group with two crystallographically distinguishable dimer units. The dimer was located in a highly symmetric circumstance; for example, its CO and C−O bonds were indistinguishable due to the presence of 2-fold rotational and mirror symmetry elements so that two hydrogen bonds should be equivalent within each dimer. Such symmetric dimer structures are very rare among carboxylic acid crystals. Stabilization of such a symmetric dimer structure is attributed probably to notably strong and angular-dependent interdimer interactions: halogen bonds and NH···O hydrogen bonds. The strength of the halogen bond, among different halogens, was in the order of I > Br > Cl from the interhalogen-atomic length as compared with its ordinary van der Waals' diameter. AIBA revealed no phase transition even down to 110 K, while AClBA revealed it at around 140 K. The difference in the thermal behaviors perhaps originates from the different strengths of halogen bonds in the AIBA and AClBA crystals.

show abstract

“…interactions of the 2-hydroxyalkyl groups contribute significantly towards tubular aggregation in alkylated derivatives of this compound. These hydrogen bonds also feature prominently in salts of DEA elucidating binding modes of thyroid hormones to transport proteins (Cody, 1981;Cody & Strong, 1980;Prout et al, 1988); the template synthesis of heterometallic wheels (Larsen et al, 2005); and in studies aimed at correlating structural and pharmacological properties of anti-inflammatory drugs (Castellari & Ottani, 1995). interactions (Table 1) to form layers parallel to the ab plane (Fig.…”

Section: S1 Commentmentioning

confidence: 99%

“…For structures of related 2-haloethylammonium salts and properties of these salts, see: Cody (1981); Cody & Strong (1980); Prout et al (1988); Castellari & Ottani (1995); de Sousa et al (2010a,b); Larsen et al (2005); Mootz et al (1989). For graph-set motifs, see: Bernstein et al (1995).…”

Section: Related Literaturementioning

confidence: 99%

Bis(2-hydroxyethyl)ammonium 2-bromophenolate

et al. 2012

View full text Add to dashboard Cite

In the crystal structure of the 1:1 title salt, C4H12NO2+·C6H4BrO−, hydrogen-bonding interactions originate from the ammonium cation, which adopts a syn conformation. A gauche relationship between the C—O and C—N bonds of the 2-hydroxyethyl fragments also facilitates O—H...O interactions of bis(2-hydroxyethyl)ammonium cation chains to phenolate O atoms. The resulting double-ion chains along [100] are further linked by N—H...O interactions, forming chains parallel to [110]

show abstract

A study of the crystal and molecular structures of phenols with only intermolecular hydrogen bonding

Cited by 30 publications

References 6 publications

Comparative molecular field analysis and synthetic validation of a hydroxyamide-propofol binding and functional block of neuronal voltage-dependent sodium channels

Comparative molecular field analysis and synthetic validation of a hydroxyamide-propofol binding and functional block of neuronal voltage-dependent sodium channels

Halogen Bond as Controlling the Crystal Structure of 4-Amino-3,5-Dihalogenobenzoic Acid and Its Effect on the Positional Ordering/Disordering of Acid Protons

Bis(2-hydroxyethyl)ammonium 2-bromophenolate

Contact Info

Product

Resources

About