Aromatic stacking – a key step in nucleation

Abstract

Crystal nucleation from solution is of central importance in the chemical and biological sciences. Linking nucleation kinetics to the properties of solutes and solvents remains a grand-challenge in physical chemistry. Through a unique dataset of compounds able to self-assemble via both hydrogen-bonds and aromatic stacking, we are able to compare the importance of these two types of interaction in driving the nucleation process. Contrary to previous reports in which solution chemistry and hydrogen bonding have been seen as controlling factors, we are now able to show that cluster growth via aromatic stacking holds the key.

The integrated DL_POLY/DL_FIELD/DL_ANALYSER software platform for molecular dynamics simulations for exploration of the synthonic interactions in saturated benzoic acid/hexane solutions

“…It has been hypothesised that both COOH H-bonding dimers andstacking interactions can be influential in directing the nucleation of molecular crystals 23,[64][65][66] . In addition to this, there have been significant experimental data reported which suggest that benzoic acid molecules pre-cluster in solution prior to nucleation, particularly evidence supporting the hypothesis that HB interactions form in solution 35,36 .…”

Investigation of an Unusual Crystal Habit of Hydrochlorothiazide Reveals Large Polar Enantiopure Domains and a Possible Crystal Nucleation Mechanism

“…Most notably,t he strongest pairwise interaction in form II is ac entrosymmetric p···p stacking interaction (À93 kJ mol À1 ), and it is considerably stronger than any pairwise interaction in form I. Acloser look at these two crystal structures reveals that this centrosymmetric p···p stacking interaction may form the junction between the enantiomorphic wings (Figure 4), and is likely to be important in the early nucleation steps that lead to the twin boundary. [24] Because P2 1 is ap olar space group,w ea lso explored the relationship between the unit-cell dipole moment (m cell )o f HCT form Ia nd the observed twin crystal habit. [24] Because P2 1 is ap olar space group,w ea lso explored the relationship between the unit-cell dipole moment (m cell )o f HCT form Ia nd the observed twin crystal habit.…”

Thermodynamic vs. Kinetic Basis for Polymorph Selection

“…Interfacial energies for organic compounds in a range of solvents vary in the range 0.3 to 10 mJ m −2 , but values as high as 40 mJ m −2 have been reported [23][24][25][26]. A limited range of interfacial energies are available for polymorph pairs.…”