Unusual effect of bulky isopropyl group on robustness of the U-motif in pyrazolo[3,4-d]pyrimidine core based 'Leonard linker' compounds in comparison to methyl/ethyl group: A1H NMR and X-ray crystallographic study

X-ray crystallographic analysis of new symmetrical 'Leonard/trimethylene linker' isopropyl analog 1,3-bis(4-isopropoxy-6-methylsulfonyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)propane (1h) does not show chain motif formed due to intermolecular C-H... 0 interactions between O atoms of sulfonyl groups and central methylene H atoms of linker along with C-H center dot center dot center dot N interactions or plus (+) motif shown earlier by corresponding methyl- (1f) and ethyl- (1g) analogs. More importantly, the more or less superimposed U-motif conformation of 1h is very different from earlier related 10 symmetrical compounds (1a-1g & 2). In 1h intramolecular folding is in such a way that whole pyrazolo[3,4-d]pyrimidine core of one side stacks more or less face-to-face on opposite side of the same molecule while in earlier compounds (1a-1g & 2) there is no intramolecular stacking between pyrazolo portions and only pyrimidine portions partially stack with each other. Surprisingly, ethyl analog (1i) of 1h again shows U-motif conformation similar to earlier related ten symmetrical compounds (1a-1g & 2). Supramolecular structures of both compounds (1h & 1i) are stabilized by weak intermolecular C-H center dot center dot center dot O, C-H center dot center dot center dot N and pi-pi interactions. (C) 2008 Elsevier B.V. All rights reserved.