Affinity of drugs and small biologically active molecules to carbon nanotubes: a pharmacodynamics and nanotoxicity...

The MM-PBSA MD method was used to estimate the affinity, as represented by log k(b), of each of a variety of biologically active molecules to a carbon nanotube in an aqueous environment. These ligand-receptor binding simulations were calibrated by first estimating the log k(b) values for eight ligands to human serum albumin, HSA, whose log k(b) values have been observed. A validation linear correlation equation was established [R(2) = 0.888, Q(2) = 0.603] between the observed and estimated log k(b) values to HSA. This correlation equation was then used to rescale all MM-PBSA MD log k(b) values using a carbon nanotube as the receptor. The log k(b) of the eight HSA ligands, nine polar and/or rigid ligands and six nonpolar and/or flexible ligands to a carbon nanotube were estimated. The range in rescaled log k(b) values across this set of 23 ligands is 0.25 to 7.14, essentially 7 orders of magnitude. Some ligands, like PGI2, bind in the log k(b) = 7 range which corresponds to the lower limits of known drugs. Thus, such significant levels of binding of biologically relevant compounds to carbon nanotubes might lead to alterations in the normal pharmacodynamic profiles of these compounds and be a source of toxicity. Ligand binding potency to a carbon nanotube is largely controlled by the shape, polarity/nonpolarity distribution and flexibility of the ligand. HSA ligands exhibit the most limited binding to a carbon nanotube, and they are relatively rigid and of generally spherical shape. Polar and/or rigid ligands bind less strongly to the carbon nanotube, on average, than nonpolar and/or flexible ligands even though the chosen members of both classes of ligands in this study have chainlike shapes that facilitate binding. The introduction of only a few strategically spaced single bonds in the polar and/or rigid ligands markedly increases their binding to a carbon nanotube.