Bioorganometallic chemistry .8. The molecular recognition of aromatic and aliphatic amino acids and substituted aromatic and aliphatic carboxylic acid guests with supramolecular (eta(5)-pentamethylcyclopentadienyl)rhodium-nucleobase, nucleoside, and nucleotide cyclic trimer hosts via non-covalent pi-pi and hydrophobic interactions in water: Steric, electronic, and conformational parameters

Molecular recognition, via non-covalent processes such as hydrogen bonding, pi-pi, and hydrophobic interactions, is an important biological phenomenon for guests, such as drugs, proteins, and other important biological molecules with, for example, host DNA/RNA. We have studied a novel molecular recognition process using guests that encompass aromatic and aliphatic amino acids [L-alanine, L-glutamine (L-Gln), L-histidine, L-isoleucine (L-Ile), L-leucine (L-Leu), L-phenylalanine (L-Phe), L-proline, L-tryptophan (L-Trp), L-valine (L-Val)], substituted aromatic carboxylic acids [o-, m-, p-aminobenzoic acids (G1-3), benzoic acid (G4), phenylacetic acid (G5), p-methoxyphenylacetic acid (G6), o-methyoxybenzoic acid (G9), o-nitrobenzoic acid (G10)], and aliphatic carboxylic acids [cyclohexylacetic acid (G7), 1-adamantanecarboxylic acid (G8)] with supramolecular, bioorganometallic hosts, (eta(5)-pentamethylcyclopentadienyl)rhodium (Cp*Rh)-nucleobase, nucleoside, and nudeotide cyclic trimer complexes, [Cp*Rh(9-methyladenine)](3)(OTf)(3) (1) (OTf = trifluoromethanesulfonate), [Cp*Rh(adenosine)](3)(OTf)(3) (2), [Cp*Rh-(2'-deoxyadenosine)](3) (OTf)3 (3), [Cp*Rh(2',3'-dideoxyadenosine)](3)(OTf)(3) (4), and [Cp*Rh(Me-5'-AMP)](3) (5), in aqueous solution at pH 7, utilizing H-1 NMR, NOE, and molecular modeling techniques, and, as well, determining association constants (K-a) and free energies of complexation (Delta G(degrees)). The host-guest complexation occurs predominantly via non-covalent pi-pi, hydrophobic, and possible subtle H-bonding interactions, with steric, electronic, and molecular conformational parameters as important criteria. Moreover, we note that both the pi-pi and hydrophobic interactions seem to be equally important when competing aromatic and aliphatic carboxylic acid guests, G5 and G7, for host 3. The solvophobic effects in H2O also control the extent of host-guest interaction and will be discussed.