BODIPY-modified Ru(II) arene complex--a new ligand dissociation mechanism and a novel strategy to red shift the photoactivation wavelength of anticancer metallodrugs.

A Ru(II) arene complex [(η(6)-p-cymene)Ru(bpy)(py-BODIPY)](PF(6))(2), where bpy is 2,2'-bipyridine and py-BODIPY is a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene dye containing a pyridine group at the 8-position, was designed and synthesized. BODIPY modification renders the monodentate pyridine ligand with long wavelength absorbing capability, and an absorption maximum at 504 nm. Upon selective irradiation of the absorption band of the py-BODIPY ligand, the dissociation of the monodentate ligand occurs efficiently, followed by substitution by 9-ethylguanine if it is present in the solution. The photoinduced ligand dissociation quantum yield was measured to be 4.1% at 480 nm. The photoinduced electron transfer from the BODIPY chromophore to the Ru(II) arene moiety plays an important role in the ligand dissociation. Such a photosensitization strategy can be utilized to develop novel anticancer metallodrugs that may respond to light in the phototherapeutic window (650-900 nm).

Small change in structure leads to large difference in protein photocleavage: two porphyrins bearing rhodanine-based pendants.

Two 5,10,15,20-tetraphenylporphyrins with one phenyl group anchored to a rhodanine-terminated side chain, RhD-TPP and RhDCOOH-TPP, were designed and synthesized, and their protein photocleavage activities were investigated using bovine serum albumin (BSA) as a model protein. Both porphyrins exhibit similar absorption spectra, fluorescence spectra, fluorescence quantum yields, and singlet oxygen ((1)O(2)) quantum yields in organic solvents due to their structure similarity. They also show similar binding affinities and binding sites toward BSA. However, RhD-TPP is nearly inactive in protein photocleavage while RhDCOOH-TPP can lead to distinct photocleavage of BSA under the same experimental conditions. Such a difference may be attributed to the different binding modes of the two porphyrin derivatives toward BSA, though the apparent binding affinities and the binding sites are similar, and consequently a great difference in the (1)O(2) quantum yields of the two porphyrins bound on BSA. The presence of the COOH group in RhDCOOH is proposed to play an important role, leading to less hydrophobic character and additional interactions towards BSA.

Oxovanadium(IV) based hypocrellin B complexes with enhanced photodynamic activity.

Hypocrellin B (HB), a naturally occurring photosensitizer, has been extensively and intensively studied as a promising photodynamic therapy (PDT) agent. In this work, three new oxovanadium(IV) complexes were designed and synthesized with HB as a bridging ligand and phen (1,10-phenanthroline, complex 1), tmp (3,4,7,8-tetramethyl-1,10-phenanthroline, complex 2) and dpq (dipyrido[3,2-f:2'3'-h]quinoxaline, complex 3) as terminal ligands. The use of a diimine terminal ligand avoids the formation of polymeric complexes and ensures the three VO(2+)-HB complexes possess a definite molecular formula and molecular weight to meet the single component requirement for an ideal PDT agent. Compared to HB, the VO(2+)-HB complexes exhibit improved water solubility, enhanced absorptivity in the phototherapeutic window, increased binding affinity toward dsDNA, and similar singlet oxygen quantum yield, therefore advanced DNA photocleavage activity. Both the DNA binding constants and photo nuclease activities of the complexes follow the order 2 (tmp) > 3 (dpq) > 1 (phen), demonstrating the importance of the binding affinity to biomolecules, which improves the bioavailability of reactive oxygen species. Our work opens a new avenue for the development of HB-based PDT agents.

Dinuclear Cu(II) hypocrellin B complexes with enhanced photonuclease activity.

Five new dinuclear Cu(II) complexes were designed and synthesized, using hypocrellin B, a naturally occurring photosensitizer that has received extensive studies as promising photodynamic therapy (PDT) agent, as bridging ligand, and five kinds of diimine ligands, including 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 3,4,7,8-tetramethyl-1,10-phenanthroline (tmp), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), and dipyrido[3,2-a:2',3'-c]phenazene (dppz), as terminal ligands, respectively. The Cu(2+)-HB complexes exhibit improved water solubility, enhanced absorptivity in the phototherapeutic window of 600-900 nm, and increased binding affinity toward dsDNA than their parent HB. The biologically accessible redox potential of Cu(II)/Cu(I) couple renders the five Cu(2+)-HB complexes chemical nuclease activities in the presence of reducing agent such as ascorbic acid. Moreover, the readily available redox potential of Cu(II)/Cu(I) couple switches the photodynamic activity from type II mechanism (singlet oxygen mechanism) for HB to type I mechanism (radical mechanism) for the Cu(2+)-HB complexes. Of the five Cu(2+)-HB complexes, complex 3-5 with terminal diimine ligands of tmp, dpq, and dppz, respectively, can photocleave supercoiled pBR322 DNA more efficiently than HB. These findings open a new avenue for the development of the HB derivatives with higher photodynamic activity and better clinical applicability.

A new Phenol Red-modified porphyrin as efficient protein photocleaving agent.

Protein affinity is of importance for porphyrins in their application in photodynamic therapy (PDT). A new Phenol Red-modified porphyrin (R-TPP) was designed and synthesized to fully take advantage of the binding character of Phenol Red towards protein. Detailed comparisons of absorption spectra, fluorescence spectra, n-octanol/water partition coefficients, (1)O(2) quantum yields, as well as protein photocleaving abilities between R-TPP and its parent porphyrin Br-TPP clearly demonstrate the benefits stemming from the modification of Phenol Red. On one hand, the presence of Phenol Red moiety greatly enhances the binding affinity of R-TPP towards model proteins (bovine serum albumin and hen egg lysozyme), and therefore improves the availability of (1)O(2). On the other hand, the presence of Phenol Red moiety provides R-TPP with amphiphilic character, and therefore restricts aggregation and favors the generation of (1)O(2). As a result, R-TPP photocleaves proteins efficiently, showing promising application potential in PDT.

[Ru(bpy)(3-n)(dpb)(n)](2+): unusual photophysical property and efficient DNA photocleavage activity.

The sequential replacement of a bpy ligand (bpy = 2,2'-bipyridine) by a dpb ligand (dpb = 2,3-bis(2-pyridyl) benzoquinoxaline) in the series [Ru(bpy)(3-n)(dpb)(n)](2+) (n = 1-3) leads to a remarkable increase of the excited state lifetime, the (1)O(2) quantum yield, and the binding affinity toward dsDNA, rendering both [Ru(bpy)(dpb)(2)](2+) and [Ru(dpb)(3)](2+) efficient DNA photocleavage activities upon red light irradiation (>or=600 nm).

A new heteroleptic ruthenium(II) polypyridyl complex with long-wavelength absorption and high singlet-oxygen quantum yield.

Ruthenium(II) polypyridyl complexes with long-wavelength absorption and high singlet-oxygen quantum yield exhibit attractive potential in photodynamic therapy. A new heteroleptic Ru(II) polypyridyl complex, [Ru(bpy)(dpb)(dppn)](2+) (bpy=2,2'-bipyridine, dpb=2,3-bis(2-pyridyl)benzoquinoxaline, dppn=4,5,9,16-tetraaza-dibenzo[a,c]naphthacene), is reported, which exhibits a (1)MLCT (MLCT: metal-to-ligand charge transfer) maximum as long as 548 nm and a singlet-oxygen quantum yield as high as 0.43. Steady/transient absorption/emission spectra indicate that the lowest-energy MLCT state localizes on the dpb ligand, whereas the high singlet-oxygen quantum yield results from the relatively long (3)MLCT(Ru-->dpb) lifetime, which in turn is the result of the equilibrium between nearly isoenergetic excited states of (3)MLCT(Ru-->dpb) and (3)pipi*(dppn). The dppn ligand also ensures a high binding affinity of the complex towards DNA. Thus, the combination of dpb and dppn gives the complex promising photodynamic activity, fully demonstrating the modularity and versatility of heteroleptic Ru(II) complexes. In contrast, [Ru(bpy)(2)(dpb)](2+) shows a long-wavelength (1)MLCT maximum (551 nm) but a very low singlet-oxygen quantum yield (0.22), and [Ru(bpy)(2)(dppn)](2+) shows a high singlet-oxygen quantum yield (0.79) but a very short wavelength (1)MLCT maximum (442 nm).

DNA photocleavage activity of cobalt(III) polypyridyl complexes containing dpq ligand.

Four cobalt(III) polypyridyl complexes, [Co(phen)(3-)(n)(dpq)(n)](3+) (phen=1,10-phenanthroline, dpq=dipyrido[3,2-f:2',3'-h]-quinoxaline) (n=0, 1, 2, and 3) were synthesized and the influences of the dpq ligand on the photophysical properties, electrochemical properties, DNA binding affinities, as well as photonuclease activities of the complexes, were examined in detail. The presence of dpq ligand increases the DNA binding affinities of the corresponding complexes remarkably with respect to [Co(phen)(3)](3+). With the sequential substitution of phen ligand by dpq ligand, the (1)O(2) quantum yields of the corresponding complexes are enhanced greatly. As a result, the photonuclease activities follow the order of [Co(dpq)(3)](3+)>[Co(phen)(dpq)(2)](3+)>[Co(phen)(2)(dpq)](3+)>>[Co(phen)(3)](3+). It was found all the examined complexes can generate ()OH upon UV irradiation, and ()OH is also involved in DNA photocleavage as reactive oxygen species.

Ruthenium(II) terpyridyl complexes exhibiting DNA photocleavage: the role of the substituent on monodentate ligand.

Five ruthenium(II) complexes, [Ru(II)(tpy)(dppz)(py-R)](2+) (tpy = 2,2':6',2''-terpyridine; dppz = dipyrido[3,2-a:2',3'-c]phenazine; py-R = 4-substituted pyridine; R = N(CH(3))(2), NH(2), OCH(3), H, NO(2)), were synthesized; and the substituent effects on the photophysical property, electrochemical property, DNA binding, and DNA photocleavage of the complexes were examined carefully. Increasing the electron-donating ability of the substituent R from NO(2) to N(CH(3))(2) leads to a cathodic shift of Ru-based oxidation potential, a red shift of the (1)MLCT absorption at room temperature and the (3)MLCT emission at 77 K, and enhancement of the DNA photocleavage ability. DNA photocleavage control experiments and the EPR spin-trapping technique confirm that the photocleavage abilities of the complexes originate from (1)O(2) production. Time-resolved absorption spectra suggest that the (3)MLCT lifetime plays an important role in the photosensitized (1)O(2) generation of these complexes, which in turn depends strongly on the electron-donating ability of the substituent R. By changing the substituent of pyridine from the electron-withdrawing to the electron-donating group, the photocleavage abilities of the complexes varied from inactive to active, providing a new strategy for the development of DNA photocleavers of tpy-based Ru(II) complexes.