Experimental and computational crystal structure landscape study of nigerloxin: a fungal metabolite from Aspergillus niger

The crystal structure landscape for the bioactive fungal metabolite, nigerloxin, has been explored in the present study using a combined experimental and computational approach. Two new solvate forms of nigerloxin, have been identified from crystallization screening experiments. Additionally, a crystal structure prediction (CSP) study of nigerloxin anhydrate and monohydrate forms has been performed in the study. A comparison of the radical scavenging properties of nigerloxin and related beta -hydroxy- gamma -pyrone analogues have been performed with the help of bond dissociation enthalpy (BDE) and HOMO-LUMO energy gap computations, which indicate the lowest BDE and HOMO-LUMO gaps for nigerloxin. Various growth units present in the experimental and predicted crystal structures were identified using the supramolecular synthon approach and were utilized in the identification of the most probable crystal growth pathways available for nigerloxin. A total of twelve distinct crystal growth pathways were identified for nigerloxin anhydrate from the CSP based crystal structural landscape study. The 1-D nigerloxin water tape synthon (1HA) was identified as the most frequently observed growth unit in the predicted structures and was also found present in the two experimental solvate forms. The higher order supramolecular constructs derived from the synthon 1HA were identified as the most probable crystal growth pathways for the nigerloxin monohydrate.