Jun-Dong Wang

Enhanced Photodynamic Efficacy of Zinc Phthalocyanine by Conjugating to Heptalysine

Zinc phthalocyanine (ZnPc) is a promising photosensitizer for photodynamic therapy, but faces some challenges: ZnPc is insoluble in water and thus requires either special formulation of ZnPc by, e.g., liposome or Cremophor EL, or chemical modification of Pc ring to enhance its bioavailability and photodynamic efficacy. Here, we conjugated monosubstituted ZnPc-COOH with a series of oligolysine moieties with different numbers of lysine residues (ZnPc-(Lys)(n) (n = 1, 3, 5, 7, 9) to improve the water solubility of the ZnPc conjugates. We measured the photosensitizing efficacies and the cellular uptakes of this series of conjugates on a normal and a cancerous cell line. In addition, we developed a sensitive in situ method to distinguish the difference in photodynamic efficacy among conjugates. Our results showed that ZnPc-(Lys)(7) has the highest photodynamic efficacy compared to the other conjugates investigated.

Cooperative lone pair–π and coordination interactions in naphthalene diimide coordination networks

Lone pair–π interaction is an important but less studied binding force. Naphthalene diimides (NDIs) are ideal to form such an interaction because their quadrupole moment is exceptionally positive. Here, we report the combination of NDI ligands bearing two divergently oriented pyridyl units with different metal nitrates in different solvents resulting in six neutral 1-D coordination networks, in which the nitrate anions not only serve as capping ligands to coordinate to metal centers but also provide lone pairs to interconnect with the π-acidic NDI ligands through lone pair–π interactions. Interestingly, such lone pair–π interactions are found to have a synergic effect on the coordination interactions of the aforementioned NDI ligands with metal ions. In other words, metal-ion-directed self-assembly of NDI ligands is supposed to be driven by cooperative lone pair–π and coordination interactions.

Structural Basis for Therapeutic Intervention of uPA/uPAR System

Urokinase-type plasminogen activator (uPA) is one of the two physiological serine proteases responsible for the activation of plasminongen to plasmin. uPA activity is regulated by its inhibitors (PAI-1 and PAI-2) and its receptor (uPAR), and an expanding list of their interacting proteins. In addition to plasminogen activation, this system also plays important roles in the regulation of many cellular processes including cell proliferation, adhesion and migration. It is beyond reasonable doubt that this enzyme system plays a central role in tumor biology and represents a high potential target for therapeutic intervention of tumor growth and metastasis. During the past fifteen years, crystal structures of uPA and its inhibitors have facilitated the development of uPA inhibitors. Many crystal structures of proteins in the uPA/uPAR system have also been reported recently, especially a series of structures of uPAR and its complexes with vitronectin and uPA, facilitating the development and evaluation of uPAR inhibitors. Recent progress on uPA inhibitors will be summarized in this article. The unique structural features and the druggable potentials of these new structures will also be discussed.

Substituted zinc phthalocyanine as an antimicrobial photosensitizer for periodontitis treatment

In the last decades the worldwide rise in antibiotic resistance has intensified the development of new antimicrobial agents. Photodynamic antimicrobial chemotherapy (PACT) has been used successfully to inactivate bacteria. We herein report a new zinc phthalocyanine based photosensitizer conjugated with polylysine moiety (ZnPc-PL). This photosensitizer significantly inactivated Porphyromonas gingivalis, the primary pathogenic bacteria responsible for periodontitis. No obvious phototoxicity was found to either mammalian bone marrow stromal cells (BMSC) or human periodontal ligament cells (HPDLC), indicating the high selectivity of ZnPc-PL toward bacteria. Furthermore, we established an experimental periodontitis model on beagle dogs to test the antimicrobial efficacy in vivo. The amount of gingival crevicular fluid (GCF) and the activity of crevicular fluid aspartate aminotransferase (AST) were monitored and were found to reduce significantly in the ZnPc-PL treated group compared to the controls (laser only and no treatment). In addition, PACT with ZnPc-PL caused a reduction in the bacterial burden by 100-fold compared to controls. Taken together, these findings suggest ZnPc-PL is a promising antimicrobial photosensitizer for the treatment of periodontal diseases.

The effect of protonation on the spectra and stabilities of alkoxyl substituted phthalocyaninatometals.

The protonation abilities of phthalocyaninatometals (MPcs) increase but their stabilities reduce by the introduction of alkoxyl substituents at alpha position. In the toluene, the order of mono-protonation rate for the tetra-alpha-(2, 2, 4-trimethyl-3-pentoxy)phthalocyaninatometals sorts with the center metals is Zn>Co>Cu>Ni>Fe, which is opposite to the order of their wavelength difference between the Q bands and X bands. However, their mono-protonated species can be decomposed easily at the rate order FePc>CoPc>CuPc>NiPc>ZnPc, analogous to their decomposition abilities in the benzoylperoxide (BPO) oxidation. In addition, it is interesting that a more remarkable decomposition is found when partial CuPc was mono-protonated.

Synthesis, spectral and electrochemical characterization of non-aggregating α-substituted vanadium(IV)-oxo phthalocyanines

Two α-substituted vanadium-oxo phthalocyanines, [(OC6H3(t-Bu)2)4Pc]VO and [(OC8H17)4Pc]VO, where OC6H3(t-Bu)2 is 2,4-di-tert-butylphenoxy and OC8H17 is 2,2,4-tri-methyl-3-pentoxy, were synthesized and characterized by elemental analysis, mass spectrometry, UV-visible, IR, ESR spectroscopy and electrochemistry. Both complexes have good solubility and do not aggregate in polar or non-polar solvents. Three reductions and two oxidations can be observed in DMF containing 0.2 M TBAP. A HOMO-LUMO gap of ~1.4 V is seen for both complexes. The first two one-electron reductions and first oxidation are reversible diffusion controlled electrode processes under the given experimental conditions. The effects of solvent and phthalocyanine macrocycle substituents on the Q bands of the electronic absorption spectra are discussed.

Coordination polymers of tetrazole-yl acylamide with octahedrally coordinated divalent transition metals: the effects of metal centers and side-groups on the structural topologies and symmetries

Hydrothermal reactions of divalent transition metal salts with two different-sized tetrazole-yl acylamide ligands, N-(1H-tetrazol-5-yl)acetamide (H-NTAA) and N-(1H-tetrazol-5-yl)propionamide (H-NTPA), led to six crystalline coordination polymers, named Cd(NTAA)2 (1), Zn(NTAA)2·∼H2O (2), Cu(NTAA)2 (3), Mn(NTAA)2 (4), Cd(NTPA)2 (5), Mn(NTPA)2 (6), respectively. The X-ray diffraction analysis revealed that compound 2 is a 1D zigzag chain, compounds 3 and 4 exhibit an interesting 2D 44-sql network, while compounds 1, 5 and 6 possess a 3D non-interpenetrated diamondoid framework. Wherein, compounds 1, 4, 5 and 6 crystallized in an acentric space group with significant second harmonic generation (SHG) efficiencies. The effect of metal ions and that of small aliphatic acyl side-groups in semirigid tetrazole-yl acylamide ligands on the structural topologies and symmetries of generated coordination polymers are discussed.

Hydrothermal synthesis of benzothiazole–carboxylic cadmium(II) coordination networks: pH-controlled topologies and compositional distributions

Using the hydrothermal synthetic method, two cadmium complexes (1 and 2) with an identical chemical formula of [Cd(ABTC)2]n (ABTC = 2-aminobenzothiazole-6-carboxylic acid) but completely different topologies were prepared at two different pH values of reaction solution, 5.3 and 7.3, respectively. Reaction with a pH in between resulted in a mixture of 1 and 2, and the ratio of two products was proportional to pH value of the reaction condition.

A convenient synthesis of a substituted phthalocyanine compound

A new substituted tetra-(4-octanethiol-5-nitro)phthalocyaninatocopper complex was synthesized by nucleophlic substitution of tetra-(4-bromo-5-nitro)phthalocyaninatocopper where the bromo activated by an ortho-nitro group is easily substituted by 1-octanethiol.

2-Benzyl­isoindoline-1,3-dione: a monoclinic polymorph

In the molecule of the title compound, C(15)H(11)NO(2), the dihedral angle between the ring systems is 81.3 (2)°. In the crystal structure, mol-ecules are held together via C-H⋯O inter-actions.