Modulating the Shape of Short Metal-Mediated Heteroleptic Tapes of Porphyrins.

In view of developing artificial light-responsive complex systems, the preparation of discrete and robust heteroleptic assemblies of different chromophores in precisely defined positions is of great value since they would allow to investigate directional processes unavailable in symmetrical architectures. Here we describe the preparation, through a modular stepwise approach, and characterization of four novel and robust metal-mediated heteroleptic 4+3 porphyrin tapes, labeled D4 -T4 -D4 , D3 -T4 -D3 , D4 -T3 -D4 , and D3 -T3 -D3 , where a central meso-tetrapyridylporphyrin (either 3'-TPyP=T3 or 4'-TPyP=T4 ) is connected to two equal cis-dipyridylporphyrins (either 3'cisDPyMP=D3 or 4'cisDPyMP=D4 ) through four {t,c,c-RuCl2 (CO)2 } fragments. Whereas D4 -T4 -D4 is flat, the tapes containing at least one 3'PyP, i. e. D3 -T4 -D3 , D4 -T3 -D4 , and D3 -T3 -D3 , have unprecedented - and well defined - 3D geometries, and each exists in solution as a pair of stereoisomers in slow conformational equilibrium. The X-ray molecular structures of two such conformers, the C-shaped (D3 -T4 -D3 )C and the z-shaped (D4 -T3 -D4 )z , were determined and are fully consistent with the solution NMR findings.

Ruthenium(II) Polypyridyl Complexes Containing Simple Dioxo Ligands: a Structure-Activity Relationship Study Shows the Importance of the Charge.

Cancer is one of the main causes of death worldwide. Platinum complexes (i. e., cisplatin, carboplatin, and others) are currently heavily used for the treatment of different types of cancer, but unwanted effects occur. Ruthenium complexes have been shown to be potential promising alternatives to these metal-based drugs. In this work, we performed a structure-activity relationship (SAR) study on two small series of Ru(II) polypyridyl complexes of the type [Ru(L1)2 (O^O)]Cln (3-8), where L1 is 4,7-diphenyl-1,10-phenantroline (DIP) or 1,10-phenantroline (phen), and O^O is a symmetrical anionic dioxo ligand: oxalate (ox, n=0), malonate (mal, n=0), or acetylacetonate (acac, n=1). These two self-consistent series of compounds allowed us to perform a systematic investigation for establishing how the nature of the ligands and the charge affect the anticancer properties of the complexes. Cytotoxicity tests on different cell lines demonstrated that some of the six compounds 3-8 have a promising anticancer activity. More specifically, the cationic complex [Ru(DIP)2 (η2 -acac)]Cl (4) has IC50 values in the mid-nanomolar concentration range, lower than those of cisplatin on the same cell lines. Interestingly, [Ru(DIP)2 (η2 -acac)]Cl was found to localize mainly in the mitochondria, whereas a smaller fraction was detected in the nucleus. Overall, our SAR investigation demonstrates the importance of combining the positive charge of the complex with the highly lipophilic diimine ligand DIP.

A Flexible Synthetic Strategy for the Preparation of Heteroleptic Metallacycles of Porphyrins.

We present a stepwise synthetic strategy for the preparation of the unprecedented heteroleptic 2+2 neutral metallacycle [{t,c,c-RuCl2(CO)2}2(4'cisDPyP)(3'cisDPyP)] (5), in which two different 5,10-meso-dipyridylporphyrins, 4'cisDPyP [i.e., 5,10-bis(4'-pyridyl)-15,20-diphenylporphyrin] and 3'cisDPyP [i.e., 5,10-bis(3'-pyridyl)-15,20-diphenylporphyrin], are joined through equal 90°-angular Ru(II) connectors. The synthesis of 5 was accomplished through the preparation of a reactive ditopic intermediate in which one of the two pyridylporphyrins is linked to two neutral ruthenium fragments, each having one residual readily available coordination site (a dmso-O). Thus, compound 5 was obtained under mild conditions through two complementary routes: either by treatment of [{t,c,c-RuCl2(CO)2(dmso-O)}2(4'cisDPyP)] (3) with 1 equiv of 3'cisDPyP or, alternatively, by treatment of [{t,c,c-RuCl2(CO)2(dmso-O)}2(3'cisDPyP)] (4) with 1 equiv of 4'cisDPyP. Heteroleptic metallacycle 5 was isolated in pure form in acceptable yield and fully characterized. Spectroscopic data and a molecular model show that 5 has an L-shaped geometry, with the two porphyrins almost orthogonal to one another. The modular approach that we established is highly flexible and opens the way to several possible exciting developments.

cis-Locked Ru(II)-DMSO Precursors for the Microwave-Assisted Synthesis of Bis-Heteroleptic Polypyridyl Compounds.

We describe a synthetic strategy for the preparation of bis-heteroleptic polypyridyl Ru(II) complexes of the type [Ru(L1)2(L2)]2+ (L1 and L2 = diimine ligands) from well-defined Ru(II) precursors. For this purpose, a series of six neutral, anionic, and cationic cis-locked Ru(II)-DMSO complexes (2-7) of the general formula [Y] fac-[RuX(DMSO-S)3(O-O)]n (where O-O is a symmetrical chelating anion: oxalate (ox), malonate (mal), acetylacetonate (acac); X = DMSO-O or Cl-; n = -1/0/+1 depending on the nature and charge of X and O-O; when present, Y = K+ or PF6-) were efficiently prepared from the well-known cis-[RuCl2(DMSO)4] (1). When treated with diimine chelating ligands (L1 = bpy, phen, dpphen), the compounds 2-7 afforded the target [Ru(L1)2(O-O)]0/+ complex together with the undesired (and unexpected) [Ru(L1)3]2+ species. Nevertheless, we found that the formation of [Ru(L1)3]2+can be minimized by carefully adjusting the reaction conditions: in particular, high selectivity toward [Ru(L1)2(O-O)]0/+ and almost complete conversion of the precursor was obtained within minutes, also on a 100-200 mg scale, when the reactions were performed in absolute ethanol at 150 °C in a microwave reactor. Depending on the nature of L1 and concentration, with the oxalate and malonate precursors, the neutral product [Ru(L1)2(O-O)] can precipitate spontaneously from the final mixture, in pure form and acceptable-to-good yields. When spontaneous precipitation of the disubstituted product does not occur, purification from [Ru(L1)3]2+ can be rather easily accomplished by column chromatography or solvent extraction. By comparison, under the same conditions, compound 1 is much less selective, thus demonstrating that locking the geometry of the precursor through the introduction of O-O in the coordination sphere of Ru is a valid strategic approach. By virtue of its proton-sensitive nature, facile and quantitative replacement of O-O in [Ru(L1)2(O-O)]0/+ by L2, selectively affording [Ru(L1)2(L2)]2+, was accomplished in refluxing ethanol in the presence of a slight excess of trifluoroacetic acid or HPF6.

Orthogonal Coordination Chemistry of PTA toward Ru(II) and Zn(II) (PTA = 1,3,5-Triaza-7-phosphaadamantane) for the Construction of 1D and 2D Metal-Mediated Porphyrin Networks.

This work demonstrates that PTA (1,3,5-triaza-7-phosphaadamantane) behaves as an orthogonal ligand between Ru(II) and Zn(II), since it selectively binds through the P atom to ruthenium and through one or more of the N atoms to zinc. This property of PTA was exploited for preparing the two monomeric porphyrin adducts with axially bound PTA, [Ru(TPP)(PTA-κP)2] (1, TPP = meso-tetraphenylporphyrin) and [Zn(TPP)(PTA-κN)] (3). Next, we prepared a number of heterobimetallic Ru/Zn porphyrin polymeric networks-and two discrete molecular systems-mediated by P,N-bridging PTA in which either both metals reside inside a porphyrin core, or one metal belongs to a porphyrin, either Ru(TPP) or Zn(TPP), and the other to a complex or salt of the complementary metal (i.e., cis,cis,trans-[RuCl2(CO)2(PTA-κP)2] (5), trans-[RuCl2(PTA-κP)4] (7), Zn(CH3COO)2, and ZnCl2). The molecular compounds 1, 3, trans-[{RuCl2(PTA-κ2P,N)4}{Zn(TPP)}4] (8), and [{Ru(TPP)(PTA-κP)(PTA-κ2P,N)}{ZnCl2(OH2)}] (11), as well as the polymeric species [{Ru(TPP)(PTA-κ2P,N)2}{Zn(TPP)}]∞ (4), cis,cis,trans-[{RuCl2(CO)2(PTA-κ2P,N)2}{Zn(TPP)}]∞ (6), trans-[{RuCl2(PTA-κ2P,N)4}{Zn(TPP)}2]∞ (9), and [{Ru(TPP)(PTA-κ3P,2N)2}{Zn9(CH3COO)16(CH3OH)2(OH)2}]∞ (10), were structurally characterized by single crystal X-ray diffraction. Compounds 4, 6, 9, and 10 are the first examples of solid-state porphyrin networks mediated by PTA. In 4, 6, 8, 9, and 11 the bridging PTA has the κ2P,N binding mode, whereas in the 2D polymeric layers of 10 it has the triple-bridging mode κ3P,2N. The large number of compounds with the six-coordinate Zn(TPP) (the three polymeric networks of 4, 6 and 9, out of five compounds) strongly suggests that the stereoelectronic features of PTA are particularly well-suited for this relatively rare type of coordination. Interestingly, the similar 1D polymeric chains 4 and 6 have different shapes (zigzag in 4 vs "Greek frame" in 6) because the {trans-Ru(PTA-κ2P,N)2} fragment bridges two Zn(TPP) units with anti geometry in 4 and with syn geometry in 6. Orthogonal "Greek frame" 1D chains make the polymeric network of 9. Having firmly established the binding preferences of PTA toward Ru(II) and Zn(II), we are confident that in the future a variety of Ru/Zn solid-state networks can be produced by changing the nature of the partners. In particular, there are several inert Ru(II) compounds that feature two or more P-bonded PTA ligands that might be exploited as connectors of well-defined geometry for the rational design of solid-state networks with Zn-porphyrins (or other Zn compounds).

Investigating the reactivity of neutral water-soluble Ru(ii)-PTA carbonyls towards the model imine ligands pyridine and 2,2'-bipyridine.

As a continuation of our strategy for preparing new Ru(ii) precursors to be exploited as building blocks in the construction of metal-mediated supramolecular assemblies with improved solubility in water, here we describe the reactivity of selected neutral Ru(ii)-PTA carbonyls (PTA = 1,3,5-triaza-7-phosphaadamantane) towards the model imine ligands pyridine (py) and 2,2'-bipyridine (bpy) and the preparation and characterization of several neutral and cationic water-soluble derivatives: trans,trans,trans-[RuCl2(CO)(py)(PTA)2] (7), cis,cis,trans-[RuCl2(CO)2(py)(PTA)] (9), cis,trans-[Ru(bpy)Cl(CO)(PTA)2]Cl (10), mer-[Ru(bpy)(CO)(PTA)3](Cl)2 (12), cis,trans-[Ru(bpy)(CO)2Cl(PTA)]Cl (13), cis,trans-[Ru(bpy)(CO)2(PTA)2](NO3)2 (14NO3). In addition, we found that light-induced isomerization in some bpy compounds could be induced. The following species, either side-products isolated in low yield or compounds obtained exclusively in solution, were also unambiguously identified: cis,cis,trans-[RuCl2(CO)(py)(PTA)2] (8), trans-[RuCl2(bpy)(CO)(PTA)] (11), cis,cis-[Ru(bpy)Cl(CO)(PTA)2]Cl (15) and cis,cis-[Ru(bpy)(CO)2Cl(PTA)]Cl (16). The X-ray structures of 7, 11·H2O, and 12·7H2O are also reported. All compounds are new and - with few exceptions - show a good solubility in water.

Rare Example of Stereoisomeric 2 + 2 Metallacycles of Porphyrins Featuring Chiral-at-Metal Octahedral Ruthenium Corners.

In this paper, we describe three new stereoisomers of the already known 2 + 2 metallacycle of porphyrins [ trans, cis, cis-RuCl2(CO)2(4' cisDPyP)]2 (2, 4' cisDPyP = 5,10-bis(4'-pyridyl)-15,20-diphenylporphyrin), namely [{ trans,cis,cis-RuCl2(CO)2}(4' cisDPyP)2{ cis,cis,cis-RuCl2(CO)2}] (14) and [ cis,cis,cis-RuCl2(CO)2(4' cisDPyP)]2 (15), in which the chiral { cis,cis,cis-RuCl2(CO)2} fragment has either a C or A handedness. The least abundant 15 exists as a mixture of two stereoisomers defined as alternate (15alt, both porphyrins are trans to a Cl and a CO) and pairwise (15pw, one porphyrin is trans to two chlorides and the other to two carbonyls), each one as a statistical mixture of meso ( AC) and racemic ( AA and CC) diastereomers. Remarkably, both 14 and 15 are-to the best of our knowledge-unprecedented examples of 2D metallacycles with octahedral chiral-at-metal connectors, and 14 is the first example of a 2 + 2 molecular square with stereoisomeric Ru(II) corners. Whereas 2 is selectively obtained by treatment of trans,cis,cis-RuCl2(CO)2(dmso-O)2 (1) with 4' cisDPyP, 14 and 15 were obtained, together with 2 (major product), using stereoisomers of 1, either cis,cis,trans-RuCl2(CO)2(dmso-S)2 (5) or cis,cis,cis-RuCl2(CO)2(dmso)2 (6), as precursors. From a general point of view, this work demonstrates that-even for the smallest 2 + 2 metallacycle and using a symmetric organic linker-several stereoisomers can be generated when using octahedral metal connectors of the type {MA2B2} that are not stereochemically rigid. As a proof-of-concept, it also opens the way to new-even though challenging-opportunities: unprecedented and yet unexplored chiral metallosupramolecular assemblies can be obtained and eventually exploited (e.g., for supramolecular catalysis) by using stereogenic octahedral metal connectors amenable to become chiral centers.