# First Crystal Structure of an Aspartame Cocrystal

## TL;DR

This paper reports the first crystal structure of an aspartame cocrystal, revealing structural features that explain its needle-like crystallization behavior.

## Contribution

The first crystal structure of an aspartame cocrystal is determined, providing insights into its challenging crystallization behavior.

## Key findings

- A cocrystal of aspartame with 4-hydroxybenzoic acid dihydrate was successfully crystallized and analyzed.
- The coformer forms an OH···–OOC synthon with aspartame in the cocrystal structure.
- The spiral structure along a 21 screw axis is responsible for the needle-like morphology of aspartame and its cocrystals.

## Abstract

Aspartame crystallizes as very long, thin needles. The
crystallization
behavior of extreme needle formers not only causes problems in industrial
processing and handling but is also of interest in fundamental research.
Cocrystallization is a popular approach to expand the solid-state
landscape of a compound and often leads to improved physicochemical
properties such as stability, dissolution behavior, particle size,
and morphology. No crystal structure of an aspartame cocrystal has
been reported in the literature up to now. In this work, a comprehensive
screening study for aspartame cocrystals was performed. Cocrystals
with fumaric acid and 4-hydroxybenzoic acid were detected by powder
X-ray diffraction analysis. Growing X-ray suitable cocrystals, however,
proved extremely difficult, as both cocrystals, like aspartame, crystallized
as very fine needles. Nevertheless, in the case of 4-hydroxybenzoic
acid, crystals of sufficient quality for single-crystal X-ray analysis
could be grown, and the first crystal structure of an aspartame cocrystal
is reported. In the cocrystal aspartame·4-hydroxybenzoic acid
dihydrate (1), the coformer forms the OH···–OOC synthon with aspartame. The aspartame zwitterions
in 1 are connected through charge-assisted NH3
+···–OOC hydrogen bonds
into a spiral along a 21 screw axis, the same structural
feature that drives the needle growth of aspartame and that seems
to be the reason why the isolation of X-ray-quality cocrystals of
aspartame is so challenging.