title: Spontaneous gelation of a novel histamine H4 receptor antagonist in aqueous solution.
abstract: OBJECTIVE
  Low molecular weight hydrogelators typically require a stimulus such as heat, antisolvent, or pH adjustment to produce a gel. This study examines gelation of a novel histamine H4 receptor antagonist that forms hydrogels spontaneously at room temperature.
  
  
  METHODS
  To elucidate the mechanism and structural moieties responsible for this unusual gelation, hydrogels were characterized by rheology, optical microscopy, and XRD. SEM was performed on xerogels; NMR measurements were conducted in gelator solutions in the presence of a gel-breaker. The influence of temperature, concentration, pH, and ionic strength on elastic and viscous moduli of the hydrogels was evaluated; gel points were established via thorough rheological criteria.
  
  
  RESULTS
  The observed are "true" gels with a fibrillar texture and lamellar microstructure. On a molecular level, the gels are composed of aggregates of partially ionized species stabilized by hydrophobic interactions of aromatic moieties. The gel-to-sol transition occurs at physiologically relevant temperatures and is concentration-, pH-, and ionic strength-dependent.
  
  
  CONCLUSIONS
  We hypothesize that this spontaneous gelation is due to the so-called "spring" effect, a high energy salt form that transiently increases aqueous solubility above its equilibrium limit. Upon equilibration, this supersaturated system undergoes aggregation that avoids crystallization and produces a hydrogel.
authors.affiliation: TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, Lexington, Massachusetts 02421, USA. alexey.popov@kalarx.com
authors.forename: Alexey
authors.initials: A
authors.lastname: Popov
authors.forename: Magali B
authors.initials: MB
authors.lastname: Hickey
authors.forename: Rupa
authors.initials: R
authors.lastname: Hiremath
authors.forename: Matthew
authors.initials: M
authors.lastname: Peterson
authors.forename: Poe
authors.initials: P
authors.lastname: Ratanabanangkoon
authors.forename: Michele
authors.initials: M
authors.lastname: Rizzolio
authors.forename: Sara
authors.initials: S
authors.lastname: Waggener
authors.forename: Yuri
authors.initials: Y
authors.lastname: Zimenkov
mesh_terms: D001288:Attention; D006633:Histamine Antagonists / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D009994:Osmolar Concentration; D044367:Phase Transition; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D012212:Rheology / Q000379:methods; D012492:Salts / Q000737:chemistry; D012996:Solutions / Q000737:chemistry; D013696:Temperature; D014867:Water / Q000737:chemistry*
chemical_list: C418607:HRH4 protein, human; D006633:Histamine Antagonists; D020100:Hydrogels; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D012492:Salts; D012996:Solutions; D014867:Water