Photo-Clickable Triazine-Trione Thermosets as Promising 3D Scaffolds for Tissue Engineering Applications.

There is an overwhelming demand for new scaffolding materials for tissue engineering (TE) purposes. Polymeric scaffolds have been explored as TE materials; however, their high glass transition state (Tg) limits their applicability. In this study, a novel materials platform for fabricating TE scaffolds is proposed based on solvent-free two-component heterocyclic triazine-trione (TATO) formulations, which cure at room temperature via thiol-ene/yne photochemistry. Three ester-containing thermosets, TATO-1, TATO-2, and TATO-3, are used for the fabrication of TE scaffolds including rigid discs, elastic films, microporous sponges, and 3D printed objects. After 14 days' incubation the materials covered a wide range of properties, from the soft TATO-2 having a compression modulus of 19.3 MPa and a Tg of 30.4 °C to the hard TATO-3 having a compression modulus of 411 MPa and a Tg of 62.5 °C. All materials exhibit micro- and nano-surface morphologies suited for bone tissue engineering, and in vitro studies found them all to be cytocompatible, supporting fast cell proliferation while minimizing cell apoptosis and necrosis. Moreover, bone marrow-derived mesenchymal stem cells on the surface of the materials are successfully differentiated into osteoblasts, adipocytes, and neuronal cells, underlining the broad potential for the biofabrication of TATO materials for TE clinical applications.

Enhanced Degradability of Thiol-Ene Composites through the Inclusion of Isosorbide-Based Polycarbonates.

Open reduction internal fixation metal plates and screws remain the established standard-of-care for complex fracture fixation. They, however, have drawbacks such as limited customization, soft-tissue adhesions, and a lack of degradation. Bone cements and composites are being developed as alternative fixation techniques in order to overcome these issues. One such composite is a strong, stiff, and shapeable hydroxyapatite-containing material consisting of 1,3,5-triazine-2,4,6-trione (TATO) monomers, which cures through high energy visible light-induced thiol-ene coupling (TEC) chemistry. Previous human cadaver and in vivo studies have shown that patches of this composite provide sufficient fixation for healing bone fractures; however, the composite lacks degradability. To promote degradation through hydrolysis, new allyl-functionalized isosorbide-based polycarbonates have been added into the composite formulation, and their impact has been evaluated. Three polycarbonates with allyl functionalities, located at the termini (aPC1 and aPC2) or in the backbone (aPC3), were synthesized. Composites containing 1, 3, and 5 wt % of aPCs 1-3 were formulated and evaluated with regard to mechanical properties, water absorption, hydrolytic degradation, and cytotoxicity. Allyl-functionalized polycaprolactone (aPCL) was synthesized and used as a comparison. When integrated into the composite, aPC3 significantly impacted the material's properties, with the 5 wt % aPC3 formulation showing a significant increase in degradation of 469%, relative to the formulation not containing any aPCs after 8 weeks' immersion in PBS, along with a modest decrease in modulus of 28% to 4.01 (0.3) GPa. Osteosyntheses combining the aPC3 3 and 5 wt % formulations with screws on synthetic bones with ostectomies matched or outperformed the ones made with the previously studied neat composite with regard to bending stiffness and strength in four-point monotonic bending before and after immersion in PBS. The favorable mechanical properties, increased degradation, and nontoxic characteristics of the materials present aPC3 as a promising additive for the TATO composite formulations. This combination resulted in stiff composites with long-term degradation that are suitable for bone fracture repair.

Antibacterial Hydrogel Adhesives Based on Bifunctional Telechelic Dendritic-Linear-Dendritic Block Copolymers.

Antibiotic-resistant pathogens have been declared by the WHO as one of the major public health threats facing humanity. For that reason, there is an urgent need for materials with inherent antibacterial activity able to replace the use of antibiotics, and in this context, hydrogels have emerged as a promising strategy. Herein, we introduce the next generation of cationic hydrogels with antibacterial activity and high versatility that can be cured on demand in less than 20 s using thiol-ene click chemistry (TEC) in aqueous conditions. The approach capitalizes on a two-component system: (i) telechelic polyester-based dendritic-linear-dendritic (DLDs) block copolymers of different generations heterofunctionalized with allyl and ammonium groups, as well as (ii) polyethylene glycol (PEG) cross-linkers functionalized with thiol groups. These hydrogels resulted in highly tunable materials where the antibacterial performance can be adjusted by modifying the cross-linking density. Off-stoichiometric hydrogels showed narrow antibacterial activity directed toward Gram-negative bacteria. The presence of pending allyls opens up many possibilities for functionalization with biologically interesting molecules. As a proof-of-concept, hydrophilic cysteamine hydrochloride as well as N-hexyl-4-mercaptobutanamide, as an example of a thiol with a hydrophobic alkyl chain, generated three-component networks. In the case of cysteamine derivatives, a broader antibacterial activity was noted than the two-component networks, inhibiting the growth of Gram-positive bacteria. Additionally, these systems presented high versatility, with storage modulus values ranging from 270 to 7024 Pa and different stability profiles ranging from 1 to 56 days in swelling experiments. Good biocompatibility toward skin cells as well as strong adhesion to multiple surfaces place these hydrogels as interesting alternatives to conventional antibiotics.

Adjunctive fixation of the humeral epicondyle in a lateral condylar fracture model: Ex vivo comparison of pins and plates with a novel composite (AdhFix).

OBJECTIVE: To compare the biomechanical properties of using a novel composite construct (AdhFix) to an interfragmentary Kirschner wire or a reconstruction plate as adjunctive epicondylar stabilization in simulated lateral unicondylar humeral fractures. STUDY DESIGN: Cadaveric biomechanical assessment. SAMPLE POPULATION: Paired humeri harvested from skeletally mature dogs (14-41 kg), nine cadavers per group. METHODS: Simulated lateral unicondylar humeral fractures were stabilized with a transcondylar 4.5 mm cortical screw placed in lag fashion. Adjunct fixations consisting of a novel composite incorporating 2.7 mm cortical screws on one side, and either a 2.7 mm reconstruction plate or a 1.6 mm Kirschner wire on the contralateral side, were tested within paired humeri. Repaired humeri were axially loaded to failure and construct stiffness, yield load, and ultimate load were obtained from the load-deformation curves. RESULTS: In pairwise comparison, yield load was significantly higher for AdhFix group compared to the pin group, p = .016. No statistical significance was seen in the comparison between AdhFix group and the plate group, p = .25. CONCLUSION: Adhfix was mechanically superior to K-wires, and comparable to plate fixation, for adjunctive fixation in a lateral humeral condylar model. Our results support further investigation of the novel composite for adjunct fracture fixation in lateral humeral condylar fractures. CLINICAL SIGNIFICANCE: The novel composite tested may be a viable alternative for adjunct fixation of humeral condylar fractures, a technique that circumvents plate contouring.

Impact of Polyester Dendrimers as Branched Multifunctional Cross-Linking Additives in Triazine-Trione-Based Composites Developed via High-Energy Visible Light Thiol-ene Chemistry.

Hydroxyapatite (HA) infused triazine-trione (TATO) composites have emerged as an injectable platform for customizable bone fixators due to their fast and benign curing via high-energy visible light-induced thiol-ene chemistry (HEV-TEC), promising mechanical performance, and preclinical outcomes. These composites can overcome many of the existing limitations accompanying metal implants such as poor patient customizability, soft tissue adhesions, and stress shielding. Taking into account that the promising benchmarked TATO composite (BC) is based on stable sulfur-carbon bonds, we herein investigate the impact of introducing polyester dendritic cross-linkers based on bis-MPA as chemically integrated branched additives that display labile esters in a branched configuration. The inclusion of dendrimers, G1 and G3, in concentrations of 1, 3, and 5 wt % in the composite formulations were found to (i) decrease the processing viscosity of the composite formulations, reaching Newtonic and nonshear thinning behavior at 37 °C and (ii) impact the size distribution of bubble cavities in the composite cross sections. The lowest collected Tg for the dendrimer-containing composites was noted to be 73.2 °C, a temperature well above physiological temperature. Additionally, all composites displayed flexural modulus above 6 GPa and flexural strength of ca. 50 MPa under dry conditions. The composites comprising 5 wt % of G1 and G3 dendrimers, with ester bond densities of 0.208 and 0.297 mmol/g, respectively, reached a mass loss up to 0.27% in phosphate buffered saline at 37 °C, which is within the range of established polycaprolactone (PCL). Combined with the nontoxic properties extracted from the cell viability study, polyester dendrimers were determined as promising additives which compatibilized well with the TATO formulation and cross-linked efficiently resulting in strong composites suited for bone fracture fixations.

Biomechanical performance of a novel light-curable bone fixation technique.

Traumatic bone fractures are often debilitating injuries that may require surgical fixation to ensure sufficient healing. Currently, the most frequently used osteosynthesis materials are metal-based; however, in certain cases, such as complex comminuted osteoporotic fractures, they may not provide the best solution due to their rigid and non-customizable nature. In phalanx fractures in particular, metal plates have been shown to induce joint stiffness and soft tissue adhesions. A new osteosynthesis method using a light curable polymer composite has been developed. This method has demonstrated itself to be a versatile solution that can be shaped by surgeons in situ and has been shown to induce no soft tissue adhesions. In this study, the biomechanical performance of AdhFix was compared to conventional metal plates. The osteosyntheses were tested in seven different groups with varying loading modality (bending and torsion), osteotomy gap size, and fixation type and size in a sheep phalanx model. AdhFix demonstrated statistically higher stiffnesses in torsion (64.64 ± 9.27 and 114.08 ± 20.98 Nmm/° vs. 33.88 ± 3.10 Nmm/°) and in reduced fractures in bending (13.70 ± 2.75 Nm/mm vs. 8.69 ± 1.16 Nmm/°), while the metal plates were stiffer in unreduced fractures (7.44 ± 1.75 Nm/mm vs. 2.70 ± 0.72 Nmm/°). The metal plates withstood equivalent or significantly higher torques in torsion (534.28 ± 25.74 Nmm vs. 614.10 ± 118.44 and 414.82 ± 70.98 Nmm) and significantly higher bending moments (19.51 ± 2.24 and 22.72 ± 2.68 Nm vs. 5.38 ± 0.73 and 1.22 ± 0.30 Nm). This study illustrated that the AdhFix platform is a viable, customizable solution that is comparable to the mechanical properties of traditional metal plates within the range of physiological loading values reported in literature.

Placenta Powder-Infused Thiol-Ene PEG Hydrogels as Potential Tissue Engineering Scaffolds.

Human placenta is a source of extracellular matrix for tissue engineering. In this study, placenta powder (PP), made from decellularized human placenta, was physically incorporated into synthetic poly(ethylene glycol) (PEG)-based hydrogels via UV-initiated thiol-ene coupling (TEC). The PP-incorporated PEG hydrogels (MoDPEG+) showed tunable storage moduli ranging from 1080 ± 290 to 51,400 ± 200 Pa. The addition of PP (1, 4, or 8 wt %) within the PEG hydrogels increased the storage moduli, with the 8 wt % PP hydrogels showing the highest storage moduli. PP reduced the swelling ratios compared with the pristine hydrogels (MoDPEG). All hydrogels showed good biocompatibility in vitro toward human skin cells and murine macrophages, with cell viability above 91%. Importantly, cells could adhere and proliferate on MoDPEG+ hydrogels due to the bioactive PP, while MoDPEG hydrogels were bio-inert as cells moved away from the hydrogel or were distributed in a large cluster on the hydrogel surface. To showcase their potential use in application-driven research, the MoDPEG+ hydrogels were straightforwardly (i) 3D printed using the SLA technique and (ii) produced via high-energy visible light (HEV-TEC) to populate damaged soft-tissue or bone cavities. Taking advantage of the bioactivity of PP and the tunable physicochemical properties of the synthetic PEG hydrogels, the presented MoDPEG+ hydrogels show great promise for tissue regeneration.

Dendritic Nanogels Directed Dual-Encapsulation Topical Delivery System of Antimicrobial Peptides Targeting Skin Infections.

Antimicrobial peptides (AMPs) are promising antibacterial agents in the fight against multidrug resistant pathogens. However, their application to skin infections is limited by the absence of a realizable topical delivery strategy. Herein, a hybrid hierarchical delivery system for topical delivery of AMPs is accomplished through the incorporation of AMPs into dendritic nanogels (DNGs) and their subsequent embedding into poloxamer gel. The high level of control over the crosslink density and the number of chosen functionalities makes DNGs ideal capsules with tunable loading capacity for DPK-060, a human kininogen-derived AMP. Once embedded into the poloxamer gel, DPK-060 encapsulated in DNGs displays a slower release rate compared to those entrapped directly in the gels. In vitro EpiDerm Skin Irritation Tests show good biocompatibility, while MIC and time-kill curves reveal the potency of the peptide toward Staphylococcus aureus. Anti-infection tests on ex vivo pig skin and in vivo mouse infection models demonstrate that formulations with 0.5% and 1% AMPs significantly inhibit the growth of S. aureus. Similar outcomes are observed for an in vivo mouse surgical site infection model. Importantly, when normalizing the bacteria inhibition to released/free DPK-060 at the wound site, all formulations display superior efficacy compared to DPK-060 in solution.

Soft Hydroxyapatite Composites Based on Triazine-Trione Systems as Potential Biomedical Engineering Frameworks.

Composites of triazine-trione (TATO) thiol-ene networks and hydroxyapatite (HA) have shown great potential as topological fixation materials for complex bone fractures due to their high flexural modulus, biocompatibility, and insusceptibility to forming soft-tissue adhesions. However, the rigid mechanical properties of these composites make them unsuitable for applications requiring softness. The scope of these materials could therefore be widened by the design of new TATO monomers that would lead to composites with a range of mechanical properties. In this work, four novel TATO-based monomers, decorated with either ester or amide linkages as well as alkene or alkyne end groups, have been proposed and synthesized via fluoride-promoted esterification (FPE) chemistry. The ester-modified monomers were then successfully formulated along with the thiol TATO monomer tris [2-(3-mercaptopropionyloxy)ethyl] isocyanurate (TEMPIC) and HA to give soft composites, following the established photo-initiated thiol-ene coupling (TEC) or thiol-yne coupling (TYC) chemistry methodologies. The most promising composite shows excellent softness, with a flexural modulus of 57 (2) MPa and εf at maximum σf of 11.8 (0.3)%, which are 117 and 10 times softer than the previously developed system containing the commercially available tri-allyl TATO monomer (TATATO). Meanwhile, the surgically convenient viscosity of the composite resins and their excellent cytotoxicity profile allow them to be used in the construction of soft objects in a variety of shapes through drop-casting suitable for biomedical applications.

Tetratopic pyrimidine-hydrazone ligands modified with terminal hydroxymethyl and acryloyl arms and their Pb(II), Zn(II), Cu(II) and Ag(I) complexes.

The first tetratopic pyrimidine-hydrazone (pym-hyz) molecular strands containing terminal hydroxymethyl (L1) and acryloyl (L2) functional groups have been synthesised. L1 was produced by step-wise imine condensation reactions, starting with 6-hydroxymethyl-2-pyridinecarboxaldehyde. L2 was then synthesised through the treatment of L1 with acryloyl chloride. NMR spectroscopy and X-ray crystallography showed that the ligands adopted a helical shape, comprised of 1 and 1/3 helical turns. Both L1 and L2 uncoiled upon reaction with an excess amount of Pb(II), Zn(II) and Cu(II) ions, resulting in linear M4LA8 complexes (where M = Pb(II), Zn(II), or Cu(II); L = L1 or L2; and A = ClO4(-), SO3CF3(-) or BF4(-)). Horse-shoe shaped Pb2LA4 complexes were also formed by reacting Pb(II) ions with either L1 or L2 in a 2 : 1 metal to ligand ratio. The addition of Ag(I) ions to either L1 or L2 resulted in Ag2L2A2 double helicates, which were stable in the presence of excess Ag(I). The Pb(II), Zn(II) and Ag(I) complexes were characterised by NMR spectroscopy, while UV-Vis spectroscopy was used to probe the Cu(II) complexes. In addition, X-ray crystallography was used to analyse the linear Pb4L1A8, horse-shoe shaped Pb2L1(ClO4)4, twisted Cu3L2(SO3CF3)6, and double helicate Ag2L12(SO3CF3)2 complexes yielding the structures [Pb4L1(ClO4)7(H2O)]ClO4·4CH3NO2 (1), [Pb4L1(SO3CF3)8]2·6CH3CN·H2O (2), [Pb2L1(ClO4)2(CH3CN)(H2O)](ClO4)2·2CH3CN·C4H10O·H2O (3), [Cu3L2(SO3CF3)3(CH3CN)2(H2O)](SO3CF3)3·2CH3CN·H2O (4) and [Ag2L12](SO3CF3)2·CH3CN·H2O (5), respectively.

Metal-induced isomerization of a molecular strand containing contradictory dynamic coordination sites.

A new hydroxymethyl terminated pyrimidine-hydrazone (pym-hyz) ligand (L1) was synthesized with a central hyz-pyridine-hyz (hyz-py-hyz) motif replacing the usual hyz-pym-hyz unit, to create a molecular strand that underwent metal-induced isomerization with a minimal net change in ligand length. NMR spectroscopy showed that L1 had a horseshoe shape due to the hyz-py-hyz and pym-hyz bonds adopting transoid conformations. The ligand was successfully reacted with Pb(II), Zn(II), and Ag(I) salts in either CH3CN or CH3NO2 resulting in horseshoe-shaped M(n+)3L1A3n (where A = ClO4(-) or SO3CF3(-)) complexes in the solution phase. Crystals were grown from these solutions, the structures of which were highly dependent on the metal ion and solvent used, and were distinctly different from those seen in solution. The crystals grown from mixtures of Pb(ClO4)2·3H2O and L1 in either CH3CN or CH3NO2 resulted in the horseshoe-shaped [Pb3L1(ClO4)4(H2O)2](ClO4)2·CH3CN (1) complex or the {[Pb3L1(ClO4)4(H2O)](ClO4)2}∞·CH3NO2 (2) helical coordination polymer, respectively. The horseshoe-shaped [Pb3L1(SO3CF3)6]·CH3CN (3) complex was crystallized from a solution of Pb(SO3CF3)2·H2O and L1 in CH3CN, while the crystals grown from the solution of Zn(SO3CF3)2 and L1 in CH3CN consisted of the zigzag-shaped [Zn3L1(H2O)7](SO3CF3)6 (4) complex. The [Ag3(L1)2](SO3CF3)3 (5) double-helicate and the macrocycle-like [Ag6(L1)2](SO3CF3)6 (6) complex were crystallized from solutions of AgSO3CF3 and L1 in either CH3CN or CH3NO2, respectively.

Influence of terminal acryloyl arms on the coordination chemistry of a ditopic pyrimidine-hydrazone ligand: comparison of Pb(II), Zn(II), Cu(II), and Ag(I) complexes.

A new ditopic pyrimidine-hydrazone ligand, 6-hydroxymethylacryloyl-2-pyridinecarboxaldehyde, 2,2'-[2,2'-(2-methyl-4,6-pyrimidinediyl)bis(1-methylhydrazone)] (L2), was synthesized with terminal acryloyl functional groups to allow incorporation into copolymer gel actuators. NMR spectroscopy was used to show that L2 adopted a horseshoe shape with transoid-transoid pym-hyz-py linkages. Metal complexation studies were performed with L2 and salts of Pb(II), Zn(II), Cu(II), and Ag(I) ions in CH3CN in a variety of metal to ligand ratios. Reacting L2 with an excess amount of any of the metal ions resulted in linear complexes where the pym-hyz-py linkages were rotated to a cisoid-cisoid conformation. NMR spectroscopy showed that the acryloyl arms of L2 did not interact with the bound metal ions in solution. Seven of the linear complexes (1-7) were crystallized and analyzed by X-ray diffraction. Most of these complexes (4-7) also showed no coordination between the acryloyl arms and the metal ions; however, complexes 1-3 showed some interactions. Both of the acryloyl arms were coordinated to Pb(II) ions in [Pb2L2(SO3CF3)4] (1), one through the carbonyl oxygen donor and the other through the alkoxy oxygen donor. One of the acryloyl arms of [Cu2L2(CH3CN)3](SO3CF3)4 (2) was coordinated to one of the Cu(II) ions through the carbonyl oxygen donor. There appeared to be a weak association between the alkoxy donors of the acryloyl arms and the Pb(II) ions of [Pb2L2(ClO4)4]·CH3CN (3). Reaction of excess AgSO3CF3 with L2 was repeated in CD3NO2, resulting in crystals of {[Ag7(L2)2(SO3CF3)6(H2O)2] SO3CF3}∞ (8), the polymeric structure of which resulted from coordination between the carbonyl donors of the acryloyl arms and the Ag(I) ions. In all cases the coordination and steric effects of the acryloyl arms did not inhibit isomerization of the pym-hyz bonds of L2 or the core shape of the linear complexes.

Sensitivity of silver(I) complexes of a pyrimidine-hydrazone ligand to solvent, counteranion, and metal-to-ligand ratio changes.

Metal complexation studies were performed with AgSO(3)CF(3) and AgBF(4) and the ditopic pyrimidine-hydrazone ligand 6-(hydroxymethyl)pyridine-2-carboxaldehyde (2-methylpyrimidine-4,6-diyl)bis(1-methylhydrazone) (1) in both CH(3)CN and CH(3)NO(2) in a variety of metal-to-ligand ratios. The resulting complexes were studied in solution by NMR spectroscopy and in the solid state by X-ray crystallography. Reacting either AgSO(3)CF(3) or AgBF(4) with 1 in either CH(3)CN or CH(3)NO(2) in a 1:1 metal-to-ligand ratio produced a double helicate in solution. This double helicate could be converted into a linear complex by increasing the metal-to-ligand ratio; however, the degree of conversion depended on the solvent and counteranion used. Attempts to crystallize the linear AgSO(3)CF(3) complex resulted in crystals with the dimeric structure [Ag(2)1(CH(3)CN)(2)](2)(SO(3)CF(3))(4) (2), while attempts to crystallize the AgSO(3)CF(3) double helicate from CH(3)CN resulted in crystals of another dimeric complex, [Ag(2)1(SO(3)CF(3))(CH(3)CN)(2)](2)(SO(3)CF(3))(2)·H(2)O (3). The AgSO(3)CF(3) double helicate was successfully crystallized from a mixture of CH(3)CN and CH(3)NO(2) and had the structure [Ag(2)1(2)](SO(3)CF(3))(2)·3CH(3)NO(2) (4). The linear AgBF(4) complex could not be isolated from the double helicate in solution; however, crystals grown from a solution containing both the AgBF(4) double helicate and linear complexes in CH(3)CN had the structure [Ag(2)1(CH(3)CN)(2)](BF(4))(2) (5). The AgBF(4) double helicate could only be crystallized from CH(3)NO(2) and had the structure [Ag(2)1(2)](BF(4))(2)·2CH(3)NO(2) (6).

Metal ion-controlled self-assembly using pyrimidine hydrazone molecular strands with terminal hydroxymethyl groups: a comparison of Pb(II) and Zn(II) complexes.

Metal complexation studies were performed with the ditopic pyrimidine-hydrazone (pym-hyz) strand 6-hydroxymethylpyridine-2-carboxaldehyde (2-methyl-pyrimidine-4,6-diyl)bis(1-methylhydrazone) (1) and Pb(ClO(4))(2)·3H(2)O, Pb(SO(3)CF(3))(2)·H(2)O, Zn(SO(3)CF(3))(2), and Zn(BF(4))(2) to examine the ability of 1 to form various supramolecular architectures. X-ray crystallographic and NMR studies showed that coordination of the Pb(II) salts with 1 on a 2:1 metal/ligand ratio in CH(3)CN and CH(3)NO(2) resulted in the linear complexes [Pb(2)1(ClO(4))(4)] (2), [Pb(2)1(ClO(4))(3)(H(2)O)]ClO(4) (3), and [Pb(2)1(SO(3)CF(3))(3)(H(2)O)]SO(3)CF(3) (4). Two unusually distorted [2 × 2] grid complexes, [Pb1(ClO(4))](4)(ClO(4))(4) (5) and [Pb1(ClO(4))](4)(ClO(4))(4)·4CH(3)NO(2) (6), were formed by reacting Pb(ClO(4))(2)·6H(2)O and 1 on a 1:1 metal/ligand ratio in CH(3)CN and CH(3)NO(2). These grids formed despite coordination of the hydroxymethyl arms due to the large, flexible coordination sphere of the Pb(II) ions. A [2 × 2] grid complex was formed in solution by reacting Pb(SO(3)CF(3))(2)·H(2)O and 1 on a 1:1 metal/ligand ratio in CH(3)CN as shown by (1)H NMR, microanalysis, and ESMS. Reacting the Zn(II) salts with 1 on a 2:1 metal/ligand ratio gave the linear complexes [Zn(2)1(H(2)O)(4)](SO(3)CF(3))(4)·C(2)H(5)O (7) and [Zn(2)1(BF(4))(H(2)O)(2)(CH(3)CN)](BF(4))(3)·H(2)O (8). (1)H NMR studies showed the Zn(II) and Pb(II) ions in these linear complexes were labile undergoing metal ion exchange. All of the complexes exhibited pym-hyz linkages in their cisoid conformation and binding between the hydroxymethyl arms and the metal ions. No complexes were isolated from reacting either of the Zn(II) salts with 1 on a 1:1 metal/ligand ratio, due to the smaller size of the Zn(II) coordination sphere as compared to the much larger Pb(II) ions.

Control of self-assembly through the influence of terminal hydroxymethyl groups on the metal coordination of pyrimidine-hydrazone Cu(II) complexes.

The synthesis and characterization of 6-hydroxymethylpyridine-2-carboxaldehyde (2-methyl-pyrimidine-4,6-diyl)bis(1-methylhydrazone) (1) is reported. Ligand 1 was designed as a ditopic pyrimidine-hydrazone molecular strand with hydroxymethyl groups attached to the terminal pyridine rings. Coordination of 1 with Cu(ClO(4))(2) x 6 H(2)O or Cu(SO(3)CF(3))(2) x 4 H(2)O in a 1:2 molar ratio resulted in the dinuclear Cu(II) complexes [Cu(2)1(CH(3)CN)(4)](ClO(4))(4) x CH(3)CN (4) and [Cu(2)1(SO(3)CF(3))(2)(CH(3)CN)(2)](SO(3)CF(3))(2) x CH(3)CN (5). X-ray crystallography and (1)H NMR NOESY experiments showed that 1 adopted a horseshoe shape with both pyrimidine-hydrazone (pym-hyz) bonds in a transoid conformation, while 4 and 5 were linear in shape, with both pym-hyz bonds in a cisoid conformation. Coordination of 1 with Cu(ClO(4))(2) x 6 H(2)O or Cu(SO(3)CF(3))(2) x 4 H(2)O in a 1:1 molar ratio resulted in three different bent complexes, [Cu(1H)(ClO(4))(2)](ClO(4)) (6), [Cu(1H)(CH(3)CN)](ClO(4))(3) x 0.5 H(2)O (7), and [Cu1(SO(3)CF(3))](2)(SO(3)CF(3))(2) x CH(3)CN (8), where the pym-hyz bond of the occupied coordination site adopted a cisoid conformation, while the pym-hyz bond of the unoccupied site retained a transoid conformation. Both 6 and 7 showed protonation of the pyridine nitrogen donor in the empty coordination site; complex 8, however, was not protonated. A variety of Cu(II) coordination geometries were seen in structures 4 to 8, including distorted octahedral, trigonal bipyramidal, and square pyramidal geometries. Coordination of the hydroxymethyl arm in the mononuclear Cu(II) complexes 6, 7, and 8 appeared to inhibit the formation of a [2 x 2] grid by blocking further access to the Cu(II) coordination sphere. In addition, the terminal hydroxymethyl groups contributed to the supramolecular structures of the complexes through coordination to the Cu(II) ions and hydrogen bonding.

2-Methyl-4,6-bis-(1-methyl-hydrazino)pyrimidine.

In the title compound, C(7)H(14)N(6), the amine groups of the two methyl-hydrazino substituents are orientated in the opposite direction to the methyl substituent at the 2-position of the pyrimidine ring. The mol-ecule is almost planar with only the two amine N atoms lying substanti-ally out of the mean plane of the pyrimidine ring [by 0.1430 (2) and 0.3092 (2) Å]. The H atoms on these amine groups point inwards towards the aromatic ring, such that the lone pair of electrons points outwards from the mol-ecule. Each mol-ecule is linked to two others through N-H⋯N hydrogen bonds between the two amino groups, forming a one-dimensional chain in the [010] direction. Offset face-to-face π-π stacking inter-actions between the pyrimidine rings organize these chains into a two-dimensional array [centroid-centroid distance = 3.789 (2) Å].