Bioorganometallic Chemistry. 8. The Molecular Recognition of Aromatic and Aliphatic Amino Acids and Substituted Aromatic and Aliphatic Carboxylic Acid Guests with Supramolecular (η⁵-Pentamethylcyclopentadienyl)rhodium−Nucleobase, Nucleoside, and Nucleotide Cyclic Trimer Hosts via Non-Covalent π−π and Hydrophobic Interactions in Water:  Steric, Electronic, and Conformational Parameters

Abstract

Molecular recognition, via non-covalent processes such as hydrogen bonding, π−π, 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, (η 5 -pentamethylcyclopentadienyl)rhodium (Cp*Rh)−nucleobase, nucleoside, and nucleotide 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 1 H NMR, NOE, and molecular modeling techniques, and, as well, determining association constants ( K a ) and free energies of complexation (Δ G °). The host−guest complexation occurs predominantly via non-covalent π−π, hydrophobic, and possible subtle H-bonding interactions, with steric, electronic, and molecular conformational parameters as important criteria. Moreover, we note that both the π−π 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 H 2 O also control the extent of host−guest interaction and will be discussed.