A spectroscopic investigation of hydrogen bond patterns in crystalline and amorphous phases in dihydropyridine calcium channel blockers.
OBJECTIVE
To gain insight into the molecular structure of amorphous compounds by investigating hydrogen bonding patterns and strength in a series of structurally related compounds. Seven 1,4-dihydropyridine calcium channel blockers were evaluated.


METHODS
FT-Raman and FT-infrared spectra of the compounds in the crystalline and amorphous states were obtained.


RESULTS
For crystalline compounds, the position of the NH vibration varied considerably. indicating that the strength of hydrogen bonding differs between the different compounds in agreement with published single crystal X-ray data. For the amorphous phases, the NH vibration occurred at approximately the same position for all compounds, suggesting a uniform average hydrogen bonding strength. Somewhat surprisingly, for some compounds, the average hydrogen bond strength in the amorphous state was found to be greater than in the crystalline compound, although for others, it was weaker as anticipated. Hydrogen bonding patterns (acceptor group) varied between the crystalline compounds, but were remarkably consistent in the amorphous compounds; thus the acceptor group in the amorphous phase is not necessarily the same as in the crystalline counterpart.


CONCLUSIONS
Hydrogen bond patterns and strength within a group of chemically related amorphous compounds were found to be very similar, but were different from those in the equivalent group of crystalline substances.
Tang
Xiaolin Charlie
XC
School of Pharmacy, University of Connecticut, Storrs 06296-2092, USA.
Pikal
Michael J
MJ
Taylor
Lynne S
LS
D002121:Calcium Channel Blockers / Q000737:chemistry*; D003460:Crystallization / Q000379:methods / Q000706:statistics & numerical data; D004095:Dihydropyridines / Q000737:chemistry*; D006860:Hydrogen Bonding; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods / Q000706:statistics & numerical data; D013059:Spectrum Analysis, Raman / Q000379:methods
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C038806:1,4-dihydropyridine