Andrea Erxleben

Structures and properties of Zn(II) coordination polymers

This review gives an overview on structures and properties of coordination polymers derived from Zn(II) and polydentate organic ligands. The versatile coordination abilities of Zn(II) allow for a wide variety of structures ranging from simple 1D infinite chains to robust, porous 3D frameworks with potential applications in sorption, separation and ion exchange. Diverse 1D, 2D and 3D architectures resulting from self-assembly of {ZnL} entities (L=organic ligand) are surveyed and their properties and potential functions are discussed.

Properties and applications of flavonoid metal complexes

Flavonoids are widely occurring polyphenol compounds of plant origin with multiple biological and chemical activities. Due to the presence of carbonyl and hydroxyl groups they can coordinate metal ions and form complexes. Metal complexes of flavonoids have many interesting properties: they are colored, often fluorescent, anti- or pro-oxidant, antimicrobial, antiproliferative and biologically active in many other ways. There are many papers covering specific aspects of activity of flavonoid metal complexes, e.g. their antioxidant properties, enzyme-mimicking behavior, therapeutic potential or use in chemical analysis. However, for a researcher interested in this theme, it would be useful to find an extensive review on more than one selected area. Our aim was to cover a wide spectrum of possible activities and potential applications of flavonoids coordinated to metal ions in order to give our readers a broad view on the topic of this class of compounds, their activity and potential applications. While a significant amount of information on the chemical properties and biological activity of flavonoid metal complexes can be found in the literature, an in-depth understanding of structure–property relationships is still lacking. In an attempt to address this issue, a comprehensive discussion of the available data is presented.

Interactions between [AuX4]− (X = Cl, CN) and cytosine and guanine model nucleobases: salt formation with (hemi-) protonated bases, coordination, and oxidative degradation of guanine

Abstract Complexes of composition AuCl3L with L = 1,9-dimethylguanine (1,9-DimeG) (1), 2-amino-6-methoxy-9-methylpurine (O6Me-9-MeG) (2), 9-methylguanine (9-MeGH) (3), and 9-ethylguanine (9-EtGH) (4) were prepared from Na[AuCl4] or H[AuCl4] and L in water at pH 3.2 ± 0.5. The X-ray crystal structures of 1 and 2 were determined. In both complexes, Au(III) binding is via N(7) of the purine ring. The coordination sphere of Au(III) is completed by three Cl ligands in a square plane and a weaker intermolecular contact with an adjacent molecule (Au···Cl, 3.59(5) A (1) and 3.48(1) A (2)), thereby making each Au atom approximately square-pyramidal. In addition, three salts containing the fully or hemiprotonated model nucleobases 7,9-dimethylguanine (7,9-DimeGH), 9-MeGH and 1-methylcytosine (1-MeC) were X-ray structurally characterized: [7,9-DimeGH][AuCl4] (5), [(9-MeGH2) · (9-MeGH)][Au(CN)4] (6), and [(1-MeCH) · (1-MeC)][Au(CN)4] · 2H2O (7). Although poorly soluble in water, compounds 1–4 redissolve in a slow process that takes weeks to months with destruction of the purine skeleton and formation of guanidinium and parabanic acid derivatives as well as other products, depending upon the conditions applied.

Magnesium Versus Zinc Coordination to Multidentate Schiff Base Ligands

The reactions of two mononuclear zinc complexes, [Zn(HL1)(H2O)2], 1, and [ZnL4(H2O)], 7, (H3L1 = Schiff base derived from 3-formylsalicylic acid and glycine, H2L4 = Schiff base derived from 2,6-diformyl-4-methylphenol and 1,2-diaminoethane), with Mg2+ has been studied. These complexes contain binucleating Schiff base ligands and have vacant coordination sites. For both compounds, substitution of zinc by magnesium has been observed in DMSO. Likewise, the Zn complex of H2L2 (Schiff base derived from salicylaldehyde and glycine) can be converted into the corresponding Mg compound. The following complexes were characterized by single-crystal X-ray analysis: [MgL3(H2O)3], 4, [MgL2(H2O)2]n, 5, [Mg(sal)2(H2O)2], 6, and [MgL4(H2O)(CH3OH)], 8 (H2L3 = Schiff base derived from 5-bromosalicylaldehyde and glycine, Hsal = salicylaldehyde). The tri- and tetradentate N,O ligands H2L3 and H2L4 form discrete complex molecules in the solid state, while a carboxylate-bridged polymeric structure is formed by H2L2. In 4 and 8 the aqua ligands hydrogen bond with the deprotonated phenolate and carboxylate oxygen atoms, resulting in the formation of dimers. In 6 two aqua ligands, two phenolate oxygens and two aldehyde oxygens give rise to an O6 coordination sphere.

Nickel(II) and cobalt(II) complexes of lidocaine: Synthesis, structure and comparative in vitro evaluations of biological perspectives.

Metal complexes of the type [Ni(LC)2(X)2], 1 and 2, [Co(LC)2(X)2], 3 and 4 (LC: lidocaine, X = dca (dicyanamide), 1 and 3, X = NCS(-), 2 and 4) have been synthesized and characterized. The geometries of 1-4 were confirmed by single crystal X-ray crystallography. The complexes are water soluble and stable in aqueous solution. The interaction of 1-4 with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) was investigated using UV-visible and fluorescence spectrophotometric methods. A gel electrophoresis assay demonstrated that the complexes cleave pUC19 plasmid DNA. The in vitro free radical scavenging, antimicrobial activity and cytotoxic potential of all the complexes were examined.

Heteronuclear μ-1-methylcytosinato-N3,N4 complexes containing very short Pt → Cu dative bonds

Abstract A series of mixed Pt11,Cu11 complexes derived from trans-[a2Pt(1-MeC-N3)2]2+ (a = NH3 or CH3NH − (1,2), OH− (3), NH3,H2O (4), coordinated to Pt via N3) and of general formula trans-[a2Pt(1-MeC−-N3,N4)2CuL]n+ with L = μ-CO 3 2− ( 1,2 ), OH − ( 3 ), NH 3 ,NH 3 H 2 O ( 4 ) , 1-MeC-N3 ( 5 ), 9-EtGH-N7,H 2 O (6) have been isolated and characterized by X-ray analysis. In all compounds a trans-a2PtII entity is bound to two cytosine nucleobases via N3 sites each, whereas a CuII is bound to two monodeprotonated N4 sites. In all cases PtII represents a ligand of CuII, which either displays a distorted square-planar (1,2,3,5) or a pentacoordinate environment (4,6). PtIICuII distances are very short, ranging from 2.49 to 2.56 A in the six compounds. EPR spectra of frozen solutions have been examined in several cases. They appear, at least for 4a and 5, to be consistent with PtCu hyperfine interactions rather than the presence of two different Cu-only species.

Nanomechanical properties of poly(lactic-co-glycolic) acid film during degradation

Despite the potential applications of poly(lactic-co-glycolic) acid (PLGA) coatings in medical devices, the mechanical properties of this material during degradation are poorly understood. In the present work, the nanomechanical properties and degradation of PLGA film were investigated. Hydrolysis of solvent-cast PLGA film was studied in buffer solution at 37 °C. The mass loss, water uptake, molecular weight, crystallinity and surface morphology of the film were tracked during degradation over 20 days. Characterization of the surface hardness and Youngs modulus was performed using the nanoindentation technique for different indentation loads. The initially amorphous films were found to remain amorphous during degradation. The molecular weight of the film decreased quickly during the initial days of degradation. Diffusion of water into the film resulted in a reduction in surface hardness during the first few days, followed by an increase that was due to the surface roughness. There was a significant delay between the decrease in the mechanical properties of the film and the decrease in the molecular weight. A sudden decline in mechanical properties indicated that significant bulk degradation had occurred.

Model of the most abundant DNA interstrand cross-link of Transplatin: X-ray structures of two modifications and H bonding behavior in the solid state and in solution of trans-[Pt(NH3)2(1-MeC-N3)(9-EtGH-N7)](ClO4)2·nH2O (1-MeC=1-methylcytosine; 9-EtGH=9-ethylguanine)

Abstract The preparation, the crystal structure determination of two modifications, and the solution behavior of the mixed nucleobase complex trans -[Pt(NH 3 ) 2 (1-MeC- N 3)(9-EtGH- N 7)](ClO 4 ) 2 · n H 2 O ( n =1.4 ( 2a ) and 0 ( 2b )) with 1-MeC=1-methylcytosine and 9-EtGH=9-ethylguanine are reported. The compound is a model for the most abundant interstrand cross-link of trans -Pt(NH 3 ) 2 Cl 2 (Transplatin) with double-stranded DNA. Characteristic features of this compound are the near-coplanarity of the two nucleobases and the intracomplex H bond between the exocyclic groups N(4)H 2 of 1-MeC and O(6) of 9-EtGH. Geometrical parameters responsible for the length of this H bond are studied. The compound can be considered a metal-modified Hoogsteen pair of cytosine and guanine. Its potential relevance to platinated DNA triplexes is also briefly discussed.

Investigation of the capacity of low glass transition temperature excipients to minimize amorphization of sulfadimidine on comilling.

The coprocessing of active pharmaceutical ingredient (API) with an excipient which has a high glass transition temperature (T(g)) is a recognized strategy to stabilize the amorphous form of a drug. This work investigates whether coprocessing a model API, sulfadimidine (SDM) with a series of low T(g) excipients, prevents or reduces amorphization of the crystalline drug. It was hypothesized that these excipients could exert a T(g) lowering effect, resulting in composite T(g) values lower than that of the API alone and promote crystallization of the drug. Milled SDM and comilled SDM with glutaric acid (GA), adipic acid (AA), succinic acid (SA), and malic acid (MA) were characterized with respect to their thermal, X-ray diffraction, spectroscopic, and vapor sorption properties. SDM was predominantly amorphous when milled alone, with an amorphous content of 82%. No amorphous content was detected by dynamic vapor sorption (DVS) on comilling SDM with 50% w/w GA, and amorphous content of the API was reduced by almost 30%, relative to the API milled alone, on comilling with 50% w/w AA. In contrast, amorphization of SDM was promoted on comilling with 50% w/w SA and MA, as indicated by near-infrared (NIR) spectroscopy. Results indicated that the API was completely amorphized in the SDM:MA comilled composite. The saturated solubility of GA and AA in the amorphous API was estimated by thermal methods. It was observed that the T(g) of the comelt quenched composites reached a minimum and leveled out at this solubility concentration. Maximum crystallinity of API on comilling was reached at excipient concentrations comparable to the saturated concentration solubility of excipient in the API. Moreover, the closer the Hildebrand solubility parameter of the excipient to the API, the greater the inhibition of API amorphization on comilling. The results reported here indicate that an excipient with a low T(g) coupled with high solubility in the API can prevent or reduce the generation of an amorphous phase on comilling.

Effects of Ball-Milling and Cryomilling on Sulfamerazine Polymorphs: A Quantitative Study

The effects of ball-milling and cryomilling on sulfamerazine forms I and II (SMZ FI, FII) were investigated using X-ray powder diffraction, infrared and near-infrared (NIR) spectroscopy. Cryomilling resulted in a complete amorphization of both polymorphs. Milling at room temperature gave mixtures of amorphous SMZ (FA) and FII. Calibration models were developed for the quantitative analysis of binary (FI/FII, FI/FA, and FII/FA) and ternary (FI/FII/FA) mixtures using NIR spectroscopy combined with partial least-squares (PLS) regression. The PLS models for binary (0%-100%), ternary (0%-100%), and low-level (0%-10%) binary mixtures had root-mean-square errors of prediction of ≤1.8%, ≤5.1%, and ≤0.80%, respectively. The calibration models were used to obtain a detailed quantitative picture of solid-state transformations during milling and any subsequent recrystallizations. FA prepared by cryomilling FI for less than 60 min recrystallized to mixtures of FI and FII, whereas samples milled for more than 60 min crystallized to pure FII. The effect of comilling SMZ with stoichiometric amounts of additives was investigated. SMZ formed amorphous materials with oxalic, dl-tartaric, and citric acids that were more stable toward recrystallization than FA. Amorphous SMZ/oxalic acid was found to recrystallize to a 2:1 cocrystal during storage.