Reactivity of ferritin and the structure of ferritin-derived ferrihydrite.

BACKGROUND: In nature or in the laboratory, the roughly spherical interior of the ferritin protein is well suited for the formation and storage of a variety of nanosized metal oxy-hydroxide compounds which hold promise for a range of applications. However, the linkages between ferritin reactivity and the structure and physicochemical properties of the nanoparticle core, either native or reconstituted, remain only partly understood. SCOPE OF REVIEW: Here we review studies, including those from our laboratory, which have investigated the structure of ferritin-derived ferrihydrite and reactivity of ferritin, both native and reconstituted. Selected proposed structure models for ferrihydrite are discussed along with the structural and genetic relationships that exist among several different forms of ferrihydrite. With regard to reactivity, the review will emphasize studies that have investigated the (photo)reactivity of ferritin and ferritin-derived materials with environmentally relevant gaseous and aqueous species. MAJOR CONCLUSIONS: The inorganic core formed from apoferritin reconstituted with varied amounts of Fe has the same structural topology as the inorganically derived ferrihydrite that is an important component of many environmental and soil systems. Reactivity of ferritin toward aqueous species resulting from the photoexcitation of the inorganic core of the protein shows promise for driving redox reactions relevant to environmental chemistry. GENERAL SIGNIFICANCE: Ferritin-derived ferrihydrite is effectively maintained in a relatively unaggregated state, which improves reactivity and opens the possibility of future applications in environmental remediation. Advances in our understanding of the structure, composition, and disorder in synthetic, inorganically derived ferrihydrite are shedding new light on the reactivity and stability of ferrihydrite derived artificially from ferritin.

Attempted Syntheses of Transition Metal and Lanthanide (Dialkylamino)squarates. The Hydrolysis Problem.

Reaction of 1-amino-2-methoxycyclobutenedione with M(NO(3))(2).xH(2)O (M = Mn, Co, Ni, Cu, Zn) in aqueous solution results in the formation of the squarates M(C(4)O(4)).4H(2)O and/or M(C(4)O(4)).2H(2)O owing to the hydrolysis of both the methoxy and amino groups on the ligand. Similarly, reaction of this ligand with M(NO(3))(3).6H(2)O (M = La, Eu, Gd, Tb) results in the formation of the respective lanthanide squarates. Buffering the reactant solutions at different pH's did not change the results and neither did using the alternative solvents methanol, ethanol, propan-1-ol, and acetonitrile. In previously reported reactions between 1-amino-2-methoxycyclobutenedione and 1-(dimethylamino)-2-methoxycyclobutenedione separately with Pb(NO(3))(2) under similar reaction conditions, the amino groups remained unhydrolyzed. The substituent amino groups also remain unhydrolyzed when these ligands are left to stand in aqueous solution in the absence of transition metal ions; only the methoxy group is hydrolyzed. 1-(Dimethylamino)-2-hydroxycyclobutenedione (1), formed from such a hydrolysis of 1-(dimethylamino)-2-methoxycyclobutenedione in aqueous solution, crystallizes in space group P2(1)/c, with a = 5.093(1) Å, b = 8.331(1) Å, c = 15.087(3) Å, beta = 95.12(1) degrees, and Z = 4. However, attempts at complexation of the ligand with Mn(II) ions resulted in the formation of a mixture of the Mn(II) squarate Mn(C(4)O(4)).4H(2)O and the salt [Mn(H(2)O)(6)][HC(4)O(3)NH(2)](2).2H(2)O (2), in which the amino group remains intact. Compound 2 crystallizes in the tetragonal space group P4(2)/m with a = 7.251(3) Å, c = 15.979(8) Å, and Z = 2. If tetraethylammonium aminosquarate is used instead of 1-amino-2-methoxycyclobutenedione, both [Co(C(4)O(4))(H(2)O)(4)] and [Co(C(4)O(4))(H(2)O)(2)] are formed on reaction with Co(NO(3))(2).6H(2)O. Hydrolysis of the amino group also occurs when the higher homologue 1-(dimethylamino)-2-methoxycyclobutenedione is reacted with Co(NO(3)).6H(2)O, but only [Co(C(4)O(4))(H(2)O)(2)] is formed. [Co(C(4)O(4))(H(2)O)(2)] crystallizes in the space group Pn&thremacr;n with a = 16.256(1) Å and Z = 24 and is isomorphous with [Co(C(4)O(4))(H(2)O)(2)].0.33H(2)O, which has been reported previously. Evidence suggests that the hydrolysis of the dialkylamino substituents in the 1-(dialkylamino)-2-methoxycyclobutenediones is apparently mediated by the transition and lanthanide metals. The use of the hydrolysis of the amino group in 1-dialkylamino derivatives of squaric acid as a convenient synthetic tool is discussed.

First-Row Transition-Metal Complexes of the 1-Methoxycyclobutenedionate(1-) Ion.

The synthesis and characterization by single-crystal X-ray crystallography of a series of monomeric first-row transition-metal complexes with the 1-methoxycyclobutenedionate(1-) ligand are described. The isomorphous compounds [M(CH(3)OC(4)O(3))(2)(H(2)O)(4)] (M = Mn, Co, Ni, Zn) are C(2) symmetric and crystallize in the monoclinic space group C2/c. The metal atom in each of these complexes is six-coordinate with two cis 1-methoxycyclobutenedionate(1-) ligands, the methoxy substituent being oriented cis with respect to the ligating oxygen atom. The remaining coordination sites are filled by four aqua ligands. Monomers are linked by O-H.O hydrogen bonds to form arrays of stepped tapes. Hydrolysis of the methoxy group on the ligand occurs during the formation of the copper complex and {[Cu(C(4)O(4))(H(2)O)(2)].0.25H(2)O}(n)() is produced. This complex crystallizes in the tetragonal space group P4/n and has a structure similar to, but differing significantly from, those of a series of 3-dimensional cage squarates which have been reported previously.

The impact of circulating cholesterol crystals on vasomotor function: implications for no-reflow phenomenon.

OBJECTIVES: The purpose of this study was to determine if cholesterol crystals can injure the endothelial surface by their jagged edges altering vasoreactivity and contributing to no-reflow after intervention. BACKGROUND: After plaque rupture, cholesterol crystals are released into the circulation and flow downstream contacting the arterial wall. METHODS: Both carotid arteries from 22 rabbits were placed in a dual perfusion chamber and challenged with norepinephrine followed by acetylcholine and nitroprusside. Arterial diameters were measured before and after exposure to cholesterol crystals or microspheres and compared with diameters of normal control arteries. Arteries were examined by light, confocal, atomic force and scanning electron microscopy. RESULTS: Pre-exposure mean arterial diameter was 2.33 ± 0.27 mm. With baseline norepinephrine there was vasoconstriction of 0.82 ± 0.19 mm, 0.79 ± 0.18 mm, and 0.83 ± 0.16 mm in lumen diameter in the crystal, microsphere, and control groups, respectively. After cholesterol crystals or microspheres, vasoconstriction was significantly less for cholesterol crystals but not for microspheres (0.71 ± 0.28 mm and 0.81 ± 0.15 mm; p < 0.02 and p = 0.68). After acetylcholine in the same artery, there was significantly less dilation before versus after crystals (0.49 ± 0.24 mm vs. 0.38 ± 0.22 mm, p = 0.04) but not with microspheres or in the control group. There was no significant difference after nitroprusside in any group, suggesting endothelial injury. By scanning electron microscopy, cholesterol crystals were found embedded in the intima with endothelial cell tears whereas the microsphere treatment and control groups had minimal or no injury (93% vs. 31% vs. 14%; p < 0.01). By atomic force microscopy, surface roughness was significantly greater with cholesterol crystals compared with microspheres or in control arteries (p < 0.05). CONCLUSIONS: Cholesterol crystals damaged the endothelium and reduced vasodilator response, potentially aggravating myocardial ischemia after interventions.

Characterization and surface reactivity of ferrihydrite nanoparticles assembled in ferritin.

Ferrihydrite nanoparticles with nominal sizes of 3 and 6 nm were assembled within ferritin, an iron storage protein. The crystallinity and structure of the nanoparticles (after removal of the protein shell) were evaluated by high-resolution transmission electron microscopy (HRTEM), atomic force microscopy (AFM), and scanning tunneling microscopy (STM). HRTEM showed that amorphous and crystalline nanoparticles were copresent, and the degree of crystallinity improved with increasing size of the particles. The dominant phase of the crystalline nanoparticles was ferrihydrite. Morphology and electronic structure of the nanoparticles were characterized by AFM and STM. Scanning tunneling spectroscopy (STS) measurements suggested that the band gap associated with the 6 nm particles was larger than the band gap associated with the 3 nm particles. Interaction of SO2(g) with the nanoparticles was investigated by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, and results were interpreted with the aid of molecular orbital/density functional theory (MO/DFT) frequency calculations. Reaction of SO2(g) with the nanoparticles resulted primarily in SO(3)2- surface species. The concentration of SO3(2-) appeared to be dependent on the ferrihydrite particle size (or differences in structural properties).

Iron and cobalt oxide and metallic nanoparticles prepared from ferritin.

Metallic Fe and Co and Fe- and Co-based oxide nanoparticles were prepared by a novel method utilizing the biologically relevant protein ferritin. In particular, iron and cobalt oxyhydroxide nanoparticles were assembled within horse spleen and Listeria innocua derived ferritin, respectively, in the aqueous phase. Ferritin containing either Fe or Co oxide was transferred and dried on a SiO2 support where the protein shell was removed during exposure to a highly oxidizing environment. It was also shown that the metal oxide particles could be reduced to the respective metal by heating in hydrogen. X-ray photoelectron spectroscopy was used to characterize the composition of the particles and atomic force microscopy was used to characterize the size of the nanoparticles. Depending on the Fe or Co loading and/or type of ferritin used, metallic and oxide nanoparticles could be produced within a range of 20-60 A.