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X-ray crystallography and NMR spectroscopy have established that copper coordinates through a 3N1O equatorial square-planar pyramid configuration: the histidine imidazole nitrogen, the glycine -amino nitrogen, and the deprotonated amide nitrogen of the glycine-histidine peptide bond, with additional oxygen coordination from neighboring complex carboxyl groups

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Many therapies now considered foundational in perioperative medicine were initially adopted based on mechanistic plausibility and early observational signals before high-quality surgical outcome trials were performed