We have designed a synthetic tetracationic metallo-supramolecular cylinder that targets the major groove of DNA with a binding constant in excess of 10 7 M ؊1 and induces DNA bending and intramolecular coiling. The two enantiomers of the helical molecule bind differently to DNA and have different structural effects. We report the characterization of the interactions by a range of biophysical techniques. The M helical cylinder binds to the major groove and induces dramatic intramolecular coiling. The DNA bending is less dramatic for the P enantiomer.W hile DNA encodes the essential blueprint for life, within biological systems its structure and function is regulated by proteins. In the postgenomic environment the goal is to understand the processing of the genetic code and how to stimulate or prevent this processing. To achieve this end a variety of different types of molecular tools will be required that recognize the genetic code in a sequence-selective fashion. Within biological systems, sequencespecific code recognition is generally achieved by the surface motifs of proteins, which generally interact noncovalently with the major groove of DNA (1-3). The major groove is particularly attractive for DNA recognition because the size and shape of the major groove of B-DNA varies most with base sequence. For example, transcriptional regulators often involve cylindrical binding units, such as ␣-helices or zinc fingers, that insert into the major groove and may kink the DNA (1-3).Oligonucleotides (synthetic and natural) can selectively recognize DNA by forming triplexes through binding in the major groove (4). Neutral oligonucleotide analogues (e.g., peptide nucleic acids) can achieve similar effects, although more commonly they achieve sequence selectivity through strand displacement (5).Such biomacromolecule recognition of DNA contrasts with synthetic small molecule recognition agents. Synthetic molecules that achieve sequence selectivity include well-known minor groove binders such as amide-linked imidazole͞pyrole oligomers and polymers (6), which in common with many small-molecule DNA-binding agents target the minor groove (7). Alternatively small molecules can act by means of intercalation (8, 9). Synthetic agents that target the major groove of DNA with recognition through noncovalent surface motifs have the potential to be a powerful new tool in the armory of reagents that is being developed to tackle the postgenomic challenge. However, to date little progress has been made in this direction, caused in large part by the size of the molecular surfaces required.DNA binding by metal complexes through formation of metal-ligand bonds (e.g., cisplatin) has been extensively studied and usually focuses on binding to N7 of G and A residues (ref. 10 and references therein). By contrast, noncovalent binding of metal complexes to DNA is a less well-developed area and has primarily centered around approximately spherical ruthenium polypyridyl complexes, complexes bearing planar intercalating units, or combinations thereof ...

The enantiomeric resolution of an extended range of di-metallo supramolecular triple-helical molecules are reported. The ligands for all complexes are symmetric with two units containing an aryl group linked via an imine bond to a pyridine. Alkyl substituents have been attached in different positions on the ligand backbone. Previous work on the parent compound, whose molecular formula is [Fe(2)(C(25)H(20)N(4))(3)]Cl4, showed that it could be resolved into enantiomerically pure solutions using cellulose and 20 mM aqueous sodium chloride. In this work a range of mobile phases have been investigated to see if the separation and speed of elution could be increased and the amount of NaCl co-eluted with the compounds decreased. Methanol, ethanol and acetonitrile were considered, together with aqueous NaCl : organic mixtures. Effective separation was most often achieved when using 90% acetonitrile : 10% 20 mM NaCl (aq) w/v, which gives scope for scaling up to incorporate the use of HPLC. The overall most efficient (i.e. fastest) separation was generally achieved where the cellulose column was packed with 20 mM NaCl (aq) and the column first eluted with 100% acetonitrile, then with 75% ethanol : 25% 20 mM NaCl (aq) until the M enantiomer had fully eluted and finally with 90% acetonitrile : 10% 20 mM NaCl (aq) until the P enantiomer had been collected. The sequence of eluents ensured minimum NaCl accompanying the enantiomers and minimum total solvent being required to elute the enantiomers, especially the second one, from the column. No helicate with a methyl group on the imine bond could be resolved and methyl groups on the pyridine rings also have an adverse effect on resolution.