Ion hydration: Implications for cellular function, polyelectrolytes, and protein crystallization

Organometallic- and organic-based materials exhibiting the technologically important property of bulk magnetism have been designed, prepared, and studied. These magnets are prepared via conventional organic chemistry methodologies and unlike conventional inorganic-based magnets do not require metallurgical processing. Furthermore, these magnets are frequently soluble in conventional solvents, and examples have saturation magnetizations exceeding that of iron metal on an Fe or mole basis. Also, magnets with critical temperatures exceeding room temperature, magnets with coercive fields exceeding that of Co5Sm, and thin-film magnets have been prepared. This article highlights the collective joint research executed in our, as well as Arthur J. Epstein's, laboratories.

Organometallic- and organic-based magnets: New chemistry and new materials for the new millennium

Mode of action of bi- and trinuclear zinc hydrolases and their synthetic analogues.

Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells and nonprostatic solid tumor neovasculature and is a target for anticancer imaging and therapeutic agents. PSMA acts as a glutamate carboxypeptidase (GCPII) on small molecule substrates, including folate, the anticancer drug methotrexate, and the neuropeptide N-acetyl-l-aspartyl-l-glutamate. Here we present the 3.5-A crystal structure of the PSMA ectodomain, which reveals a homodimer with structural similarity to transferrin receptor, a receptor for iron-loaded transferrin that lacks protease activity. Unlike transferrin receptor, the protease domain of PSMA contains a binuclear zinc site, catalytic residues, and a proposed substrate-binding arginine patch. Elucidation of the PSMA structure combined with docking studies and a proposed catalytic mechanism provides insight into the recognition of inhibitors and the natural substrate N-acetyl-l-aspartyl-l-glutamate. The PSMA structure will facilitate development of chemotherapeutics, cancer-imaging agents, and agents for treatment of neurological disorders.

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Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase

Unusual dimers with wide interplanar separations, that is, very long bonds with dD ≈ 3.05 A, are common to the spontaneous self-association of various organic π-radicals in solution and in the crystalline solid state, independent of whether they are derived from negatively charged anion radicals of planar electron acceptors (TCNE-•, TCNQ-•, DDQ-•, CA-•), positively charged biphenylene cation-radical (OMB+•), or neutral phenalene radical (PHEN•). All dimeric species are characterized by intense absorption bands in the near-IR region that are diagnostic of the charge-transfer transitions previously identified with intermolecular associations of various electron-donor/acceptor dyads. The extensive delocalizations of a pair of π-electrons accord with the sizable values of (i) the enthalpies (−ΔHD) and entropies (−ΔSD) of π-dimerization measured by quantitative UV−vis/EPR spectroscopies and (ii) the electronic coupling element Hab evaluated from the strongly allowed optical transitions, irrespective of whether...

Stable (Long-Bonded) Dimers via the Quantitative Self-Association of Different Cationic, Anionic, and Uncharged π-Radicals: Structures, Energetics, and Optical Transitions

https://epublications.marquette.edu/cgi/viewcontent.cgi?article=1337&context=chem_fac

The 1.20 Å Resolution Crystal Structure of the Aminopeptidase from Aeromonas proteolytica Complexed with Tris: A Tale of Buffer Inhibition

The aminopeptidase from Aeromonas proteolytica (AAP) contains two zinc ions in the active site and catalyzes the degradation of peptides. Herein we report the crystal structures of AAP at 0.95-A resolution at neutral pH and at 1.24-A resolution at low pH. The combination of these structures allowed the precise modeling of atomic positions, the identification of the metal bridging oxygen species, and insight into the physical properties of the metal ions. On the basis of these structures, a new putative catalytic mechanism is proposed for AAP that is likely relevant to all binuclear metalloproteases.

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The high-resolution structures of the neutral and the low pH crystals of aminopeptidase from Aeromonas proteolytica.

Synthons Tl1[TCNE]*- (1) and Tl12[TCNE]2- (2), for [TCNE]*- and [TCNE]2-, respectively, in metathesis reactions have been quantitatively prepared and characterized. The structure of 1 was solved and refined in a monoclinic unit cell at 27 degrees C [C2/c, a = 12.6966 (12) angstroms, b=7.7599 (7) angstroms, c=15.5041 (15) angstroms, beta = 96.610 (5) degrees , V= 1517.4 (2) angstroms3, Dcalcd = 2.911 gcm-3, Z=8, R1 = 0.0575, omegaR2=0.0701] and exhibits nuCN absorptions at 2,191 (s) and 2,162 (s) cm-1 consistent with metal-bound [TCNE]*-. The structure of 1 consists of a distorted square antiprismatic octacoordinate Tl1 bound to six monodentate [TCNE]*-s with TlN separations ranging from 2.901 to 3.171 angstroms averaging 3.020 angstroms, and one bidentate [TCNE]*- with TlN separations averaging 3.279 angstroms. The TlN bonding is attributed to electrostatic bonding. The [TCNE]*-s form dimerized zigzag chains with intra- and interdimer separations of 2.87 and 3.29 angstroms, respectively. The tight pi-[TCNE](2)2- dimer is diamagnetic and has the shortest intradimer [TCNE]*- distance reported. These synthons for [TCNE]*- and [TCNE]2- in metathesis reactions lead to the precipitation of, for example, TlIX (X = Cl, Br, OAc). Reaction of 1 with MnIII(porphyrin)X (X = Cl, OAc) forms the molecule-based magnets of [MnIII(porphyrin)][TCNE] composition, while the reaction of [CrI(C6H6)2]Br and (Me2N)2CC(NMe2)2Cl2, [TDAE]Cl2, with 1 forms [CrI(C6H6)2] [TCNE] and [TDAE][TCNE]2, respectively. The structure of [TDAE][TCNE]2.MeCN was solved and refined in an orthorhombic unit cell at 21 degrees C [I222, a = 10.2332(15), b = 13.341(6), c = 19.907(8) angstroms, V= 2717.7 angstroms3, Z = 4; Dcalcd = 1.216 gcm-3, R=0.083, Romega = 0.104] and exhibits upsilonCN absorptions at 2,193 (m), 2,174 (s), and 2,163 (s) cm-1 consistent with isolated [TCNE](2)2- , in contrast to the aforementioned TlI bound [TCNE](2)2-. The reaction of 2 with [TDAE]Cl2 forms [TDAE]2+[TCNE]2-.

Synthesis and Reactivity of the TlI salts of [TCNE].− and [TCNE]2−: The Structural Determination of TlI[TCNE] and [TDAE][TCNE]2 and Evidence for a Chelated [TCNE].−

Reaction of 1-amino-2-methoxycyclobutenedione with M(NO3)2·xH2O (M = Mn, Co, Ni, Cu, Zn) in aqueous solution results in the formation of the squarates M(C4O4)·4H2O and/or M(C4O4)·2H2O owing to the hydrolysis of both the methoxy and amino groups on the ligand. Similarly, reaction of this ligand with M(NO3)3·6H2O (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(NO3)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-hydroxycyclob...

William Desmarais

Papers

The 1.20 Å Resolution Crystal Structure of the Aminopeptidase from Aeromonas proteolytica Complexed with Tris: A Tale of Buffer Inhibition

The high-resolution structures of the neutral and the low pH crystals of aminopeptidase from Aeromonas proteolytica.

Synthesis and Reactivity of the TlI salts of [TCNE].− and [TCNE]2−: The Structural Determination of TlI[TCNE] and [TDAE][TCNE]2 and Evidence for a Chelated [TCNE].−

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