caa a22 4500 445313102 CHVBK 20180317142637.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s11095-011-0483-9 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0483-9 Spontaneous Gelation of a Novel Histamine H4 Receptor Antagonist in Aqueous Solution [Elektronische Daten] [Alexey Popov, Magali Hickey, Rupa Hiremath, Matthew Peterson, Poe Ratanabanangkoon, Michele Rizzolio, Sara Waggener, Yuri Zimenkov] ABSTRACT: Purpose: 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. Springer Science+Business Media, LLC, 2011 gelation nationallicence low molecular weight hydrogels nationallicence rheology nationallicence supramolecular assembly nationallicence xerogels nationallicence Popov Alexey TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, 02421, Lexington, Massachusetts, USA aut Hickey Magali TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, 02421, Lexington, Massachusetts, USA aut Hiremath Rupa TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, 02421, Lexington, Massachusetts, USA aut Peterson Matthew TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, 02421, Lexington, Massachusetts, USA aut Ratanabanangkoon Poe TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, 02421, Lexington, Massachusetts, USA aut Rizzolio Michele Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, 92121, San Diego, California, USA aut Waggener Sara TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, 02421, Lexington, Massachusetts, USA aut Zimenkov Yuri TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, 02421, Lexington, Massachusetts, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/10(2011-10-01), 2556-2566 0724-8741 28:10<2556 2011 28 11095 https://doi.org/10.1007/s11095-011-0483-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0483-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Popov Alexey TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, 02421, Lexington, Massachusetts, USA aut NATIONALLICENCE 700 1- Hickey Magali TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, 02421, Lexington, Massachusetts, USA aut NATIONALLICENCE 700 1- Hiremath Rupa TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, 02421, Lexington, Massachusetts, USA aut NATIONALLICENCE 700 1- Peterson Matthew TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, 02421, Lexington, Massachusetts, USA aut NATIONALLICENCE 700 1- Ratanabanangkoon Poe TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, 02421, Lexington, Massachusetts, USA aut NATIONALLICENCE 700 1- Rizzolio Michele Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, 92121, San Diego, California, USA aut NATIONALLICENCE 700 1- Waggener Sara TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, 02421, Lexington, Massachusetts, USA aut NATIONALLICENCE 700 1- Zimenkov Yuri TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, 02421, Lexington, Massachusetts, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/10(2011-10-01), 2556-2566 0724-8741 28:10<2556 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer