Surface-enhanced Raman scattering (SERS) spectra from phosphonate derivatives of N-heterocyclic aromatic compounds immobili ed on an electrochemically roughened sil er electrode surface are reported and compared to Raman spectra of the corresponding solid species. The tested compounds contain imida ole ImMeP ([hydroxy-(1H-imidazol-5-yl)-methyl]-phosphonic acid) and (ImMe) (bis[hydroxy-(1H-imidazol-4-yl)-methyl -phosphinic acid; thia ole BAThMeP ((butylamino-thiazol-2-yl-methyl)-phosphonic acid) and BzAThMeP ((benzylamino-thiazol-2-yl-methyl)-phosphonic acid)]; and pyridine ((PyMe) (bis[(hydroxy-pyridin-3-yl-methyl-phosphinic acid aromatic rings. Changes in wa enumber broadness, and the enhancement of N-heterocyclic aromatic ring bands upon adsorption are consistent with the adsorption primarily occurring through the N lone pair of electrons with the ring arranged in a largely edge-on manner for ImMeP and BzAThMeP or in a slightly inclined orientation to the silver electrode surface at an intermediate angle from the surface normal for (ImMe), BAThMeP, and (PyMe). A strong enhancement of a roughly 1500 cm(-1) SERS signal for ImMeP and (PyMe) is also observed. This phenomenon is attributed to the formation of a locali ed C=C bond, which is accompanied by a decrease in the ring-surface pi-electrons o erlap. In addition, more intense SERS bands due to the ben ene ring in BzAThMeP are observed than those observed for the thia ole ring, which suggests a preferential adsorption of bell ene. Some interaction of a phosphonate unit is also suggested but with moderate strength between biomolecules. The strength of the P=O coordination to the sil er electrode is highest for ImMeP but lowest for BzAThMeP. For all studied biomolecules, the contribution of the structural components to their ability to interact with their receptors was con-elated with the SERS patients.