The interaction between human adult hemoglobin (Hb) and bare US quantum dots (QDs) was investigated by fluorescence, synchronous fluorescence, circular dichroism (CD), and Raman spectroscopic techniques under physiological pH 7.43. The intrinsic fluorescence of Hb is statically quenched by US QDs. The quenching obeys the Stern-Volmer equation, with an order of magnitude of binding constant (K) of 10(7). The electrostatic adsorption of Hb on the cationic US QDs surface is energetically favorable (Delta S-0 = 70.22 Jmol(-1) K-1, Delta H-0 = -23.11 kJ mol(-1)). The red shift of synchronous fluorescence spectra revealed that the microenvironments of tryptophan and tyrosine residues at the alpha(1)beta(2) interface of Hb are disturbed by US QDs, which are induced from hydrophobic cavities to a more exposed or hydrophilic surrounding. The secondary structure of the adsorbed Hb has a loose or extended conformation for which the content of a-helix has decreased from 72.5 to 60.8%. Moreover, Raman spectra results indicated that the sulfur atoms of the cysteine residues form direct chemical bonds on the surface of the US QDs. The binding does not significantly affect the spin state of the heme iron, and deoxidation is not expected to take place on the coated oxyhemoglobin. The change of orientation of heme vinyl groups was also detected. (c) 2007 Elsevier Inc. All rights reserved.