H-1 NMR studies were performed on two beta-carboline derivatives interacting with human serum albumin. The spin-lattice relaxation rates of the two derivatives, having side chains of different length and polarity, were used to demonstrate a diverse motional behavior in solution together with slightly different relaxation pathways. Single-and double-selective excitation made it possible to evaluate dynamics in the free and protein-bound states. Occurrence of a relatively long hydrophilic chain interacting with the proton-acceptor nitrogen of the beta-carboline moiety was shown to yield lower association constants, slower dissociation rates, and diverse interacting modes with the indole hydrophobic site of the protein. (C) 1998 Academic Press.