Under lab conditions, xDNA orients itself in the syn conformation. This unfortunately does not expose the binding face of the xDNA nucleotides to face the neighbouring strand for binding, meaning that extra measures must be applied to alter the conformation of xDNA before attempting to form helices. However, the anti and syn orientations are practically identical energetically in expanded bases. This conformational preference is seen primarily in pyrimidines, and purines display minimal preference for orientation.