The past few decades of molecular recognition studies have greatly enhanced our knowledge on apolar, ion-dipole, and hydrogen-bonding interactions. However, much less attention has been given to the role that multipolar interactions, in particular those with orthogonal dipolar alignment, play in organizing a crystal lattice or stabilizing complexes involving biological receptors. By using results from database mining, this review attempts to give an overview of types and structural features of these previously rather overlooked interactions. A number of illustrative examples of these interactions found in X-ray crystal structures of small molecules and protein-ligand complexes demonstrate their propensity and thus potential importance for both, chemical and biological molecular recognition processes.

A series of 5'-linked stilbene-DNA conjugates with different substituents in the distal aromatic ring of the stilbene was prepared, and the effect of the modifications on duplex stability was determined via UV-melting curves. A trimethoxystilbene derivative as a 5'-substituent increases duplex melting points by up to 12.2 degrees C per modification. With this alkoxystilbene substituent, terminal mismatches in DNA duplexes lower the melting point by up to 23.4 degrees C over the perfectly matched control, whereas terminal mismatches in unmodified DNA cause melting point depressions of no more than 6.1 degrees C. An aminomethylstilbene substituent linked to an oligopyrrolamide minor groove binder increases the melting point of an all-A/T decamer by up to 32.7 degrees C, thus shifting the melting point into a range typical for duplexes with statistical G/C-content. An affinity- and selectivity-enhancing effect was also observed when the trimethoxystilbene cap was employed on a small DNA microarray. The phosphoramidite of the trimethoxystilbene can be readily employed in automatic DNA synthesis, facilitating the generation of DNA chips with improved fidelity.

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In our molecular recognition studies, aimed at quantifying the energetics of individual protein-ligand interactions, [1] we became interested in exploring cation-p interactions [2,3] in the D-pocket of thrombin, a central serine protease in the blood coagulation cascade. The bottom of this hydrophobic pocket is lined by the indole residue of Trp 215 (Figure 1), an aromatic amino acid side chain frequently involved in cationp interactions in biological systems.[4] To probe this interaction, we prepared the tricyclic inhibitors [5] (AE )-1 and (AE )-2, predicted by computer modeling [6] to position a quaternary ammonium ion and an uncharged tert-butyl group above the indole ring of Trp 215.The synthesis of (AE )-1 started with the 1,3-dipolar cycloaddition between maleimide 3, aldehyde 4, and l-proline (5) to give (AE )-6, which was transformed into amidinium salt (AE )-7 using a Pinner-reaction (Scheme 1, for full experimen-

The ability to control the structure of monolayers on radial and faceted surfaces is an important goal for the successful application of nanoparticles in devices and materials. To investigate the effect of steric bulk in the monolayer periphery on monolayer protected gold cluster (MPC) properties, we have synthesized a series of gold nanoparticles having amide functionality within the monolayer chains and altering the peripheral end groups of the monolayer. Investigation of these MPCs using IR spectroscopy and cyanide-mediated decomposition of the gold core reveals a strong correlation between the strength of the intramonolayer hydrogen bonding and the maximal decomposition rate. Additionally, comparison with corresponding ester-functionalized derivatives indicates that the hydrogen bonding amide unit in the monolayer emphasizes the effects of the peripheral groups on monolayer surface packing and MPC properties.