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Laccase mimics are multicopper oxidase highly important for biotechnology and environmental evaluation/remediation. However, buffer species-dependent catalytic activity is rarely investigated. Herein, through Cu2+ coordinating with adenine (A), gram-scale Cu-Adenine nanosheets are synthesized. As a laccase mimic, Cu-Adenine exhibits excellent catalytic performance in 10 mM Tris-HAc, and greatly decreases in 10 mM MES (4-morpholine ethanesulfonic acid) and further decreases in 10 mM HEPES (N-2-hydroxyethyl piperazine-N'-2-ethanesulfonic ac