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Jacqueline K. Barton

Publications and source records attributed to Jacqueline K. Barton.

4 recordsLinked to original sources
PubMed1999

Spectral and Structural Characterization of 5,6-Chrysenequinone Diimine Complexes of Rhodium(III): Evidence for a pH-Dependent Ligand Conformational Switch.

Rhodium(III) complexes containing 9,10-phenanthrenequinone diimine (phi) ligands have been broadly applied for the construction of DNA binding and recognition molecules, and more recently, derivatives containing the 5,6-chrysenequinone diimine (chrysi) ligand have been shown specifically to recognize base mismatches in DNA. Here the structural properties of [Rh(bpy)(2)(chrysi)]Cl(3) and spectroscopic properties of derivatives are examined and compared to those of phi complexes of rhodium. Although similar in many respects, phi and chrysi complexes display distinctly different protonation behavior. The pK(a) values of chrysi complexes are as much as 1 unit lower than analogous phi compounds, and visible spectra of the chrysi complexes differ markedly from the phi counterparts in acidic but not basic solution. This protonation behavior is traced to the presence of a steric clash between a proton on the aromatic ring of the chrysi ligand and the acidic immino proton of the metal complex. In avoidance of this steric clash, a significant disruption in the planarity of the chrysi ligand is evident crystallographically in the structure of [Rh(bpy)(2)(chrysi)]Cl(3).3CH(3)CN.2H(2)O (triclinic crystal system, space group P&onemacr; (No. 2), Z = 2, a = 9.079(3) Å, b = 10.970(3) Å, c = 21.192(8) Å, alpha = 86.71(3) degrees, beta = 89.21(3) degrees, gamma = 78.58(3) degrees, V = 2065.4(12) Å(3)). Phi complexes, lacking the additional aromatic ring, require no similar distortion from ligand planarity. NMR spectra support this pH-dependent structural distortion for the chrysi complex. Rhodium complexes of chrysenequinone diimine, therefore, not only represent new DNA binding molecules targeted to mismatches but also provide an illustration of a pH "gated" ligand conformational switch.

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PubMed1998

Functionalized Rhodium Intercalators for DNA Recognition.

A series of rhodium complexes containing the phenanthrenequinone diimine (phi) ligand have been prepared which bind DNA by intercalation and, upon photoactivation, promote DNA strand breaks. In this series, the ancillary, nonintercalating bipyridyl or phenanthroline ligands have been functionalized to yield complexes containing guanidinium, amido, or amino groups arranged with defined stereochemistry for site-specific interaction with the DNA bases. Lambda-1-[Rh(MGP)(2)phi](5+) (MGP = 4-(guanidylmethyl)-1,10-phenanthroline) site-specifically targets the 6-base pair sequence 5'-CATATG-3' with a binding affinity of 1 (+/-0.5) x 10(8) M(-)(1) while Delta-1-[Rh(MGP)(2)phi](5+) displays an affinity of 5 (+/-2) x 10(7) M(-)(1) for 5'-CATCTG-3'. Even though these two isomers target sites which differ by only a single base, binding is highly enantioselective. The specificity is derived chiefly from interactions of the pendant guanidinium groups with the DNA bases. For the racemates of 1-[Rh(GEB)(2)phi](5+) (GEB = (4-(2-guanidylethyl)-4'-methyl-2,2'-bipyridine) and 1-[Rh(GPB)(2)phi](5+) (GPB = (4-(2-guanidylpropyl)-4'-methyl-2,2'-bipyridine), photocleavage patterns also show the strongest site of photocleavage as 5'-CATCTG-3', the target site for Delta-1-[Rh(MGP)(2)phi](5+). Moreover, consistent with the dominance of the guanidinium groups in establishing specificity, significantly enhanced photocleavage is evident for the 1-positional isomer of these complexes, where the guanidinium moieties are directed toward the DNA (above and below the phi ligand) compared to the 2-isomer, in which the guanidinium groups are directed away from the DNA. In contrast to Lambda-1-[Rh(MGP)(2)phi](5+), Lambda-1-[Rh(GEB)(2)phi](5+) shows little cleavage at 5'-CATATG-3'; this sensitivity to linker length likely depends on the mode of recognition of 5'-CATATG-3' involving sequence-dependent unwinding of the DNA site. Analogous site-specificity or isomer-specificity is not evident with the complexes which contain pendant amido or amino functionalities. Instead these complexes appear to resemble the parent, unfunctionalized [Rh(phen)(2)phi](3+) with respect to recognition. Pendant guanidinium functionalities appear to be particularly advantageous in the construction of small molecules which bind DNA with site-specificity.

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PubMed1998

Ru(phen)(2)dppz(2+) Luminescence: Dependence on DNA Sequences and Groove-Binding Agents.

Emission of Delta-Ru(phen)(2)dppz(2+) bound to nucleic acid polymers of different sequence has been investigated by time-resolved luminescence spectroscopy and the effect of major and minor groove DNA binding agents on the luminescence profile of the complex evaluated. In the presence of a 1:1 mixture of poly d(AT) and poly d(GC), the excited-state decay of Delta-Ru(phen)(2)dppz(2+) can be described by a linear combination of the decay profiles in the presence of poly d(AT) and poly d(GC) independently. This analysis indicates that approximately 85% of the complexes are bound to poly d(AT) and that the metallointercalator preferentially occupies AT sites in mixed-sequence polymers such as calf thymus or T4 DNA. When rac-Ru(phen)(2)dppz(2+) bound to [d(5'-GAGTGCACTC-3')(2)] is titrated with the major groove intercalator Delta-alpha-[Rh[(R,R)-Me(2)trien]phi](3+), the ruthenium emission yield decreases while the absorbance of the pi-pi transition centered on the dppz ligand increases, until saturation behavior is observed at a 1:1 Rh/duplex ratio. These titrations indicate that Ru(phen)(2)dppz(2+) is displaced from the major groove by the rhodium complex. In contrast, for rac-Ru(phen)(2)dppz(2+) bound to poly d(AT), addition of the minor groove binding agent distamycin produces an increase in ruthenium emission which saturates at approximately 1 distamycin/5 bp, consistent with the double helix being able to accommodate major and minor groove binders simultaneously. Distamycin has no effect on the emission of Ru(phen)(2)dppz(2+) emission bound to poly d(GC). These photophysical studies establish a sequence preference in binding to DNA by Ru(phen)(2)dppz(2+) as well as providing support for the original assignment by NMR of ruthenium intercalation from the major groove side of the DNA helix.

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