Fine Tuning the Hydrophobicity of a New Three-Dimensional Cu2+ MOF through Single Crystal Coordinating Ligand Exchange Transformations.

The synthesis, characterization, and single-crystal-to-single-crystal (SCSC) exchange reactions of a new 3D Cu2+ MOF based on 5-aminoisophthalic acid (H2AIP), [Cu6(µ3-ΟΗ)3(ΑΙΡ)4(HΑΙΡ)]n·6nDMF·nH2O - UCY-16·6nDMF·nH2O, are reported. It exhibits a 3D structure based on two [Cu4(µ3-OH)2]6+ butterfly-like secondary building units, differing in their peripheral ligation, bridged through HAIP-/AIP2- ligands. This compound displays the capability to exchange the coordinating ligand(s) and/or guest solvent molecules through SCSC reactions. Interestingly, heterogeneous reactions of single crystals of UCY-16·6nDMF·nH2O with primary alcohols resulted not only in the removal of the lattice DMF molecules but also in an unprecedented structural alteration that involved the complete or partial replacement of the monoatomic bridging µ3-OH- anion(s) of the [Cu4(µ3-OH)2]6+ butterfly structural core by various alkoxy groups. Similar crystal-to-crystal exchange reactions of UCY-16·6nDMF·nH2O with long-chain aliphatic alcohols (CxH2x+1OH, x = 8-10, 12, 14, and 16) led to analogues containing fatty alcohols. Notably, the exchanged products with the bulkier alcohols UCY-16/n-CxH2x+1OH·S' (x = 6-10, 12, 14, and 16) do not mix with H2O being quite stable in this solvent, in contrast to the pristine MOF, and exhibit a hydrophobic/superhydrophobic surface as confirmed from the investigation of their water contact angles and capability to remove hydrophobic pollutants from aqueous media.

Dual-Emissive Rectangular Supramolecular Pt(II)-p-Biphenyl with 4,4'-Bipyridine Derivative Metallacycles: Stepwise Synthesis and Photophysical Properties.

Mixed-ligand tetranuclear supramolecular coordination complexes (SCCs) of Pt(II)-p-biphenyl and bridging ligands derivatives of 4,4'-bypiridine (8)-(10), were synthesized and characterized. The SCCs were synthesized stepwise, starting from the Pt-p-biphenyl -Pt core. The crystal structure of complex {[Pt(2,2'-bpy)]4(µ-bph)2(µ-(4,4'-bpy)2}{PF6}4 (2,2'-bpy = 2,2'-bipyridine, bph = p-biphenyl and 4,4'-bpy = 4,4' bipyridine), was determined using single-crystal diffraction methods. The emission profile of the tetranuclear complexes (8)-(10) was influenced by the length of the bridging ligands and was found to depend on solvent polarity. Dual-emission patterns in methanol-water mixtures were observed only in the cases of complexes (9) and (10), attributed to aggregation-induced emission phenomena.

Synthesis and Characterization of Ruthenium-Paraphenylene-Cyclopentadienyl Full-Sandwich Complexes: Cytotoxic Activity against A549 Lung Cancer Cell Line and DNA Binding Properties.

Novel full-sandwich (η5-Cp)-Ru-paraphenylene complexes with the general formula [(η5-Cp)nRu(η6-L)](PF6)n where n = 1-3 and L = biphenyl, p-terphenyl and p-quaterphenyl, were synthesized and characterized by means of spectroscopic and analytical techniques. The structures of the complexes [(η5-Cp)Ru(η6-biphenyl)](PF6) (1), [(η5-Cp)Ru(η6-terphenyl)](PF6) (3) and [(η5-Cp)2Ru(η6-terphenyl)](PF6)2 (4) was determined by X-ray single crystal methods. The interaction of the complexes [(η5-Cp)Ru(η6-quaterphenyl)]Cl, (6)Cl, and [(η5-Cp)2Ru(η6-quaterphenyl)]Cl2, (7)Cl2, with the DNA duplex d(5'-CGCGAATTCGCG-3')2 was studied using NMR techniques. The results showed that both complexes interacted non-specifically with both the minor and major grooves of the helix. Specifically, (6)Cl exhibited partial binding through intercalation between the T7 and T8 bases of the sequence without disrupting the C-G and A-T hydrogen bonds. Fluorometric determination of the complexes' binding constants revealed a significant influence of the number of connected phenyl rings in the paraphenylene ligand (L) on the binding affinity of their complexes with the d(5'-CGCGAATTCGCG-3')2. The complexes (6)Cl and (7)Cl2 were found to be highly cytotoxic against the A549 lung cancer cell line, with complex (6) being more effective than (7) (IC50 for (6)Cl: 17.45 ± 2.1 µΜ, IC50 for (7)Cl2: 65.83 ± 1.8 µΜ) and with a selectivity index (SI) (SI for (6)Cl: 1.1 and SI for (7)Cl2: 4.8).

Synthesis, characterization, interactions with the DNA duplex dodecamer d(5'-CGCGAATTCGCG-3')2 and cytotoxicity of binuclear η6-arene-Ru(II) complexes.

The novel binuclear η6-arene-Ru(II) complexes with the general formula {[(η6-cym)Ru(L)]2(µ-BL)}(PF6)4, and their corresponding water soluble {[(η6-cym)Ru(L)]2(µ-BL)}Cl4, where cym = p-cymene, L = 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen), BL = 4,4'-bipyridine (BL-1), 1,2-bis(4-pyridyl)ethane (BL-2) and 1,3-bis(4-pyridyl)propane (BL-3), were synthesized and characterized. The structure of {[(η6-cym)Ru(phen)]2(µ-BL-1)}(PF6)4 was determined by X-ray single crystal methods. The interaction of {[(η6-cym)Ru(phen)]2(µ-BL-i)}Cl4 (i = 1, 2, 3; (4), (5) and (6) correspondingly) with the DNA duplex d(5'-CGCGAATTCGCG-3')2 was studied by means of NMR techniques and fluorescence titrations. The results show that complex (4) binds with a Kb = 12.133 × 103 M-1 through both intercalation and groove binding, while (5) and (6) are groove binders (Kb = 2.333 × 103 M-1 and Kb = 3.336 × 103 M-1 correspondingly). Comparison with the mononuclear complex [(η6-cym)Ru(phen)(py)]2+ reveals that it binds to the d(5'-CGCGAATTCGCG-3')2 with a Kb value two orders of magnitude lower than (4) (Kb = 0.158 × 103 M-1), indicating that for the binuclear complexes both ruthenium moieties participate in the binding. The complexes were found to be cytotoxic against the A2780 and A2780 res. cancer cell line with a selectivity index (SI) in the range of 3.0-5.9.

Stepwise synthesis, characterization, DNA binding properties and cytotoxicity of diruthenium oligopyridine compounds conjugated with peptides.

Although the interactions of oligopyridine ruthenium complexes with DNA have been widely studied, the biological activity of similar diruthenium oligopyridine complexes conjugated with peptides has not been investigated. Herein, we report the stepwise synthesis and characterization of diruthenium complexes with the general formula [(La)Ru(tppz)Ru(Lb)]n+ (tppz = 2,3,5,6-tetra(2-pyridyl)pyrazine, La = 2,2':6',2''-terpyridine or 4-phenyl-2,2':6',2''-terpyridine and Lb = 2,2':6',2''-terpyridine-4'-CO(Gly1-Gly2-Gly3-LysCONH2) (5), (6), n = 5; 2,2':6',2''-terpyridine-4'-CO(Gly1-Gly2-Lys1-Lys2CONH2) (7), (8), n = 6; 2,2':6',2''-terpyridine-4'-CO(Ahx-Lys1Lys2CONH2) (9), (10), n = 5, Ahx = 6-aminohexanoic acid). The compounds [(trpy)Ru(tppz)Ru(trpy-CO2H)](PF6)4, (2)(PF6)4, [(ptrpy)Ru(tppz)Ru(trpy-CO2H)](PF6)4, (3)(PF6)4 and [(ptrpy)Ru(tppz)Ru(trpy)](PF6)4, (4)(PF6)4 were also characterized by single crystal X-ray methods. Moreover, the interactions of the chloride salts (5), (6) and (4) with the self-complementary dodecanucleotide duplex d(5'-CGCGAATTCGCG-3')2 were studied by NMR spectroscopic techniques. The results show that complex (4) binds in the central part of the oligonucleotide, from the minor groove through the ligand ptrpy, while the ligand trpy, which was located on the other side of the diruthenium core, does not contribute to the binding. Complex (5) binds similarly, through the ligand ptrpy. However, the induced upfield shifts of the ptrpy proton signals are significantly lower than the corresponding ones in the case of (4), indicating much lower binding affinity. This is clear evidence that the tethered peptide Gly1-Gly2-Gly3-Lys1CONH2 hinders the complex binding, even though it contains groups that are able to assist it (e.g., the positively charged amino group of lysine, the peptidic backbone, the terminal amide). Complex (6) shows a non-specific binding, interacting through electrostatic forces. The chloride salts of (4), (5) and (6) had insignificant effects on the cell cycle distribution and marginal cytotoxicity (IC50 > 750 µM) against human lung cancer cell lines H1299 and H1437, indicating that their binding to the oligonucleotide is not a sufficient condition for their cytotoxicity.

Synthesis, reactivity and characterization of Pt(ii) complexes with N,N' chelating ligands; structure and dimethylsulfoxide reactivity relationship.

Platinum(ii) complexes of the formula PtLCl2 [L = 2-(2'-pyridyl)quinoxaline, (pqx) (1), 2,(2'-pyridyl)benzo[g]quinoxaline, (pbqx) (3) and 2,(2'-pyridyl)quinoline, (pqn) (5)] were synthesized and characterized by spectroscopic and X-ray diffraction methods. Also, monodentate coordination of the ligands pqx and pbqx formed the complexes trans-Pt(DMSO)pqxCl2 (2) and trans-Pt(DMSO)pbqxCl2 (4) as it is indicated from X-ray crystal structure and NMR studies. The reaction of the complexes (1), (3) and (5) with DMSO-d6 revealed a ligand-release solvolysis, which was studied by means of NMR techniques. Correlation between the crystal structures of (1), (3), and (5) and the kinetic or thermodynamic parameters of the solvolysis reactions showed that the tendency of the ligands pqx, pbqx, and pqn to return to the anti-configuration in addition to their ability to form non-classical H-bonds are crucial factors for the ligand-release solvolysis. Instantaneous DMSO-d6 solvolysis for the complexes (1) and (3) and slow kinetics solvolysis for (5) (k = 10-4 ± 6.4 × 10-6 s-1) reflect their structural differences in ligand planarity. Based on NMR techniques a two-step mechanism of the chelate ring opening was suggested with equilibrium constants of the overall reaction at 298 K, Keq = 4.1 ± 0.2 × 10-4 M-1 (1) and Keq = 1.7 ± 0.2 × 10-4 M-1 (2).

Interactions of Trivalent Lanthanide Cations with a New Hexadentate Di-Schiff Base: New Lanthanide(III) Complexes from (NE,N'E)-2,2'-(ethane-1,2-diylbis(oxy))bis(N-(pyridin-2-ylmethylene)ethanamine).

The novel lanthanide(III) complexes [Ln(NO(3))(2)L](NO(3)).3MeOH (Ln = La 1, Pr 2) and [Ln(NO(3))(3)L](NO(3)).2MeOH (Ln = Gd 3, Yb 4), where L = (NE,N'E)-2,2'-(ethane-1,2-diylbis(oxy))bis(N-(pyridin-2-ylmethylene)ethanamine), have been obtained by direct reaction of the Schiff base ligand and the corresponding hydrated lanthanide(III) nitrates in methanol. All complexes were characterized spectroscopically and thermogravimetrically. Complex 4 was also characterized with crystallographic studies: orthorhombic P2(1)2(1)2(1), a = 10.6683(14), b = 13.4752(15), c = 19.3320(26) A. In the molecular structure of 4, Yb(III) is surrounded by all donor atoms of the Schiff base (four nitrogen and two oxygen atoms) and four oxygen atoms belonging to two bidentate chelating nitrato ligands.

Interpenetrated networks from a novel nanometer-sized pseudopeptidic ligand, bridging water, and transition metal ions with cds topology.

The combination of a new pseudopeptidic ligand, transition metal ions, and bridging water molecules results in the formation of [M(mu-TBG)(mu-H2O)(H2O)2].2H2O (M: Cu, Co and H2TBG: terephthaloylbisglycine); both compounds show rare two-fold interpenetrated three-dimensional cds-nets and reversible loss of coordinated and lattice water molecules.

An extremely stable Ni(II) complex derived from the hydrolytic cleavage of the C-terminal tail of histone H2A.

The C-terminal blocked tetrapeptides SHHK- and SAHK-, which represent the fragments produced from the hydrolysis of the hexapeptides' -TASHHK-, -TESHHK-, and -TESAHK- complexes with Ni(II), were synthesized and their interactions with Ni(II) ions were studied potentiometrically and spectroscopically. Both tetrapeptides interact strongly with Ni(II) ions leading to square-planar complexes with 4N {NH(2),2N(-),N(im)} coordination. The stability of the Ni-SHHK- complex is about 2 orders of magnitude higher than the Ni-SAHK- complex. Spectroscopic evidence and theoretical predictions suggest the positioning of the free imidazole ring, in the Ni-SHHK- complex, above the coordination plane, explaining the extra stability of the complex.

Interactions of Ni(II) and Cu(II) ions with the hydrolysis products of the C-terminal -ESHH- motif of histone H2A model peptides. Association of the stability of the complexes formed with the cleavage of the -E-S- bond.

We studied the interactions of Ni(II) and Cu(II) ions with the synthetic tetrapeptides SHHK- and SAHK-, which were blocked by amidation making them more realistic models of the hydrolysis peptidic products of the hexapeptides models of H2A histone. A combination of potentiometric and spectroscopic techniques (UV/Vis, CD, NMR and EPR) suggested that at pH > 7 both tetrapeptides coordinated equatorially through the imidazole ring of His in position 3, the N-terminal amino group and the two amide nitrogens existing between these groups {NH2, 2N-, NIm} forming 4N square-planar complexes. While in the case of the CuH(-1)L complex with SHHK- a possible axial coordination of the imidazole ring of His in position 2 was suggested, in the case of the analogous NiH(-1)L complex a completely different interaction of the same ring with metal ions was observed. As expected these complexes have the same structures with the hydrolysis products produced from the Ni(II)- or Cu(II)-assisted hydrolysis of previously studied hexapeptide models of the C-terminal of histone H2A, due to their predominance at pH > 7.4. In addition, the competition plots presented herein showed that the synthetic tetrapeptides SHHK- and SAHK- have higher affinity towards Ni(II) and Cu(II) ions than the previously studied hexapeptides, suggesting that metal ions remain bound to the peptidic products during the hydrolysis cleavage. Thus, it can be concluded that the stability of Ni(II) or Cu(II) complexes with the synthetic tetrapeptides and consequently with the real hydrolysis peptidic products is the driving force of the hydrolysis reaction of H2A histone blocked hexapeptide models, presented in previous studies.

Interactions of Zn(II) ions with three His-containing peptide models of histone H2A.

The interactions of Zn(ll) ions with the blocked hexapeptide models -TESHHK-, -TASHHK- and -TEAHHK- of the -ESHH- motif of the C-terminal of historic H2A were studied by using potentiometric and IH-NMR techniques. The first step of these studies was to compare the pKa values of the two His residues inside each hexapeptide calculated by potentiometric or H-NMR titrations. Hereafter, the potentiometric titrations in the pH range 5 11 suggest the formation of several monomeric Zn(ll) complexes. It was found that all hexapeptides bind to Zn(ll) ions initially through both imidazole nitrogens in weakly acidic and neutral solutions forming slightly distorted octahedral complexes. At higher pH values, the combination of potentiometric titrations and one and two dimensional NMR suggested no amide coordination in the coordination sphere of Zn(II) ions. Obviously, these studies support that the -ESHH- sequence of histone H2A is a potential binding site for Zn(II) ions similarly with the Cu(II) and Ni(ll) ions, presented in previous papers.