AbstractThe synthesis of self‐assembly systems that can mimic partial biological behaviours require ingenious and delicate design. For decades, scientists are committed to exploring new base pairing patterns using hydrogen bonds directed self‐assembly of nucleotides. A fundamental question is the adaptive circumstance of the recognition between base pairs, namely, how solvent conditions affect the domain of base pairs. Towards this question, three nucleotide complexes based on 2’‐deoxycytidine‐5’‐monophosphate (dCMP) and cytidine‐5’‐monophosphate (CMP) were synthesized in different solvents and pH values, and an unusual cytosine‐cytosine base paring pattern (named full C : C base pairing) has been successfully obtained. Systematic single crystal analysis and 1H NMR titration spectra have been performed to explore factors influencing the formation of base paring patterns. Moreover, supramolecular chirality of three complexes were studied using circular dichroism (CD) spectroscopy in solution and solid‐state combined with crystal structure analysis.