Here we present SERS spectra of several
l-phenylalanine (Phe) phosphonodipeptides, i.e.,
l-Phe-
l-Ala-PO
3H
2 (
MD1),
l-Phe-
l-Va
l-PO
3H
2 (
MD2),
l-Phe-β-Ala-CH(OH)-PO
3H
2 (
MD3),
l-Phe-
l-Ala-CH(OH)-PO
3H
2 (
MD4),
l-Ala-(3,4-dimethoxy)-
l-Phe-PO
3H
2 (
MD5), and
l-Ala-(3,4-dimethoxy)-(des-CH
2)-
l-Phe-PO
3H
2 (
MD6), immobilized on
electrochemically roughened silver electrodes. These spectra are analyzed by theoretical calculations using density functional theory (DFT) at the B3LYP level with 6-31++G** basis set. In addition, these spectra are compared with SERS spectra of these species adsorbed on a colloidal
silver surface. We showed that on the macroscopic
silver substrate, the Phe aromatic ring of
MD3 and
MD4 is oriented vertically, while for
MD1 it almost “stands up” on this surface. In the other three cases, the Phe ring adopts a tilted orientation in regard to the
substrate. We also find that the phosphonate
, methyl/methane, or dimethoxy groups of
MD1,
MD2,
MD3,
MD5, and
MD6 are involved in the interaction of these phosphonodipeptides with the
electrochemically roughened surface. This phenomenon is clearly seen for –CH
2–/–CH
3/–OCH
3 moieties as well as for the
group that adsorbs on the macroscopic
silver substrates mainly via the P
O fragment. We also showed that
MD4 binds to the macroscopic
silver substrate through the hydroxyl, amine, and phosphonate groups, while the methylene/methane moieties are remote from this surface. We found that studied phosphonodipeptides often adsorb differently on the macroscopic
silver substrate and on the colloidal
silver nanoparticles. For example,
MD1 adopts an almost vertical orientation on the
electrochemically roughened silver substrate and is tilted or close to flat on the
silver nanoparticles.