Poster Abstracts - 2016

Application of SQUEEZE to solve a crystal structure of a model of a molybdenum cofactor. Sandy Eagle, East Tennessee State University.

Abstract: Molybdenum cofactors (MoCo) are required for the function of wide variety of enzymes. Models of MoCo allow the study and elucidation of structural details which facilitate understanding. We received a crystalline sample of a MoCo model as a request for service crystallography. The monoclinic crystal (C2/c) of C17H18ClMoS2O5 solved well with the exception of a disordered molecule of solvent (apparently DMSO) in the lattice. Attempts to resolve the disorder with static models resulted in an R1 of 6.29% and a GooF of 1.09. Attempts to leave in the DMSO in the lattice, but assign it a half occupancy, for example, resulted in a lower R value, but an unrealistic solution. Application of SQUEEZE resulted in a refinement with a R1 of 2.30 % and a GooF of 1.17.


Binding of Nitrogenase Relevant Substrates to Iron-Sulfur Sites. Anna Brosnahan, Yale University. 

Abstract: Nitrogenase enzymes perform biological conversion of N2 to ammonia at metal clusters containing iron sites with sulfur and carbon based ligands. The details of the mechanism remain unknown, however Fe-N2 and Fe-NxHy complexes supported by sulfur, or by sulfur and carbon ligands, are probably crucial intermediates. We use simple synthetic complexes to model potential structures and examine chemical reactivity of such species. A simple iron model system based on sulfur and carbon ligands mimics Fe-S dissociation and N2 binding in nitrogenase. Additionally, the same bis(thiolate) ligand system enables preparation of various Fe-NxHy complexes. 


Catalytic Water Oxidation with Manganese Complexes of a Novel NNO-donor Ligand. Thoe K Michaelos, Yale University.

Abstract: Manganese is the metal found in the oxygen evolving complex (OEC) of the natural water-splitting enzyme Photosystem II. There is great interest in developing water-splitting catalysts from manganese due to its low cost, high abundance, and biological relevance. To date, the most active manganese-based functional model of the OEC is the "Mn terpy dimer" [Mn2O2(terpy)2(H2O)2]3+ (terpy = 2,2':6',2"-terpyridine). However, none of the proposed higher oxidation state intermediates has been observed; the highest state isolated is Mn(IV,IV) ,which does not participate in the catalytic cycle. 

Our group has shown that pyridine-alkoxide is enormously successful as a ligand for water oxidation (WO) catalysts due to its ability to stabilize high oxidation states and its resistance to oxidation. Pyridine-alkoxide ligands were screened with Mn for water-splitting activity, and Mn complexes of an NNO-donor ligand, bipy-alk (bipy-alk = 2-([2,2'bipyridin]-6-yl)propan-2-ol) were found to catalytically evolve oxygen over long periods of time when driven with the chemical oxidant KHSO5. The active species is proposed to be a di-μ-oxo dimer similar to the terpy dimer. Several crystal structures of products formed in the reaction have been isolated. Any intermediates observed or isolated may provide insight for the mechanisms of both the Mn terpy dimer and the OEC.


Dinitrogen functionalization by iron beta-diketiminate complexes enhanced through alkali metal cation chelation. Sean McWilliams, Yale University.

Abstract: Functionalization of dinitrogen provides biologically available nitrogen containing molecules, such as ammonia, that are required for life. The nitrogenase enzymes and the Haber-Bosch process, the two major methods of nitrogen fixation, have cationic species (charged amino acid residues and alkali metal cations respectively) that may influence Fe-N2 interactions. The roles of these charged species in the stepwise reduction of the strong N-N triple bond remain speculative. This presentation describes the role of alkali metal cations in N2 activation and functionalization in beta-diketiminate supported bimetallic iron-dinitrogen complexes that contain close interactions between cations and bound dinitrogen. Chelation of the alkali metal cations leads to a new terminal N2-binding mode previously unobserved in this system. The terminal-N2 complex is significantly more reactive than the bridging bimetallic system leading to shorter reaction times and higher yields of products in which the N2 unit is functionalized.


Exploring high oxidation state complexes and catalysts for water oxidation using an oxidation resistant N, O- donor ligand. Shashi Bhushan Sinha, Yale University.

Abstract: We describe facial and meridional isomers of [RhIII(pyalk)3], as well as meridional [RhIV(pyalk)3]+ {pyalk = 2-(2-pyridyl)-2-propanoate}, the first coordination complex of rhodium in an N,O-donor environment to show a clean, reversible III-IV redox couple and to have a stable Rh(IV) form, which we characterize by EPR and UV-visible spectroscopy and X-ray crystallography. The unprecedented stability of the Rh(IV) species is ascribed to both the exceptional donor strength of the ligands, their oxidation-resistance and the mer geometry. Additionally, we have synthesized and crystallographically characterized an Ir(IV,IV)-mono-mu-oxo complex with pyalk. The Ir complex is active for homogeneous water oxidation using sodium periodate as the chemical oxidant.


Exploring Lanthanide Extended Structures and Aqueous Polyoxometalate Ions: Bridging Solid- and Solution-State Chemistries. Eric M. Villa, Creighton University.

Abstract: Polyoxometalate ions are an enormous class of metal-oxide clusters with extensive applications; however, the aqueous solution reaction dynamics of these ions are underexplored and many fundamental questions remain unanswered. We are particularly interested in how the solid-state structures of the polyoxometalate ion influences the solution-state properties, such as stability, protonation and oxygen exchange kinetics. Here we will discuss the crystal structures and the reaction dynamics of small molybdenum based polyoxometalates in aqueous solution. 

Additionally, we are interested in the formation of lanthanide extended structures with simple redox active oxoanions. Here we are controlling the composition of the starting solutions (varying counterions, ligand concentrations and pH) to hydrothermally synthesize these compounds. Currently we are focusing on three redox active ligands: sulfite, thiosulfate and phosphite. Along with exploring the in-situ hydrothermal redox chemistry, the resulting products have the potential to form structures with useful properties, such as non-linear optical properties, due to the polarizability of the ligands. Herein, we report the resulting products of these room temperature and hydrothermal syntheses.


Ribosome Inactivating Peptides and the common mechanism of inhibition. Raktim Roy, Yale University.

Abstract: Bacterial resistance to clinically used drugs is becoming a major public health concern. Proline-rich antimicrobial peptides (PrAMPs) have kindled renewed interests due to their targeted inhibitory effect on the bacterial protein synthesis, making them effective therapeutic leads, against human pathogens. 

Here, we report crystal structures at less than 3 Å resolution for a set of PrAMPs, providing insights into their mode of ribosome inactivation and translation inhibition1. These ribosome-inactivating polypeptide (RIPs) sterically interfere with the tRNAs in the A and P sites and also occlude the peptide exit tunnel of the bacterial ribosome. We purified 70S ribosomes from Thermus thermophilus, which were then co-crystallized with mRNA, tRNAs and RIPs. We used X-ray on all our crystals containing the complexes to collect diffraction patterns form which we solved the structures by molecular replacement methods. Our biochemical experiments show that the ribosome was effectively stalled during translation right after the initiation step, in presence of the RIPs. This inhibition was also equally potent in cellular environment and was reflected in corresponding hindered cell growth and MIC values in very low micro-molar ranges. We also found from the high-resolution structures, that all of these RIPs have a common mode of binding and their spatial architecture inside the Ribosome overlaps with the binding sites of three well-known classes of antibiotics, a feature that would markedly reduce the probability of appearance of drug resistance. These structures and biochemical data will provide a strong platform for structure-based design of new-generation therapeutics against pathogenic microbes.


Self-assembling peptide nucleic acids. Linda Shimon, Weizmann Institute of Science.

Abstract: Examples of molecular self-assembly are widespread in the biological world. DNA can spontaneously form helices and peptides can assemble to nanotubes and fibrils. Artificially synthesized peptide nucleic acid hybrids (PNA) combine the physical and structural properties of both chemical families.


Substitution at allylic stereogenic centers of a [13]-macrodilactone: effects on macrocyclization efficiency and topology. Kelli Rutledge1, Anniefer N. Magpusao1, Brandon Q. Mercado2, Mark W. Peczuh1, University of Connecticut1 and Yale University2.

Abstract: Macrocycles are attractive scaffolds for the development of new bioactive compounds. They balance the target affinity and specificity associated with biopolymers with favorable physicochemical properties associated with small molecules. Central to this behavior is the shape of a macrocycle; it is a fundamental parameter that makes a macrocycle able to bind its target. Our program is geared at understanding the factors that dictate the shape and topology of macrocycles, especially the relationship between the configuration of individual stereogenic centers and planar chirality. The [13]-macrodilactones we study are composed of three four-atom planar units (two esters and an E-alkene) and a one-atom "hinge". We previously evaluated stereogenic centers associated with the ester units, both on the chain attached to the ester oxygen and the carbon a- to the carbonyl. Here we evaluate using X-ray crystallography the consequences of substitution at the positions allylic to the E-alkene, which are β- to the ester carbonyl. We are not only looking at the effect substituents have on the shape at the allylic position, but also the effect it has on the efficiency of ring closing metathesis (RCM). RCM is a common macrocyclization strategy but there are several factors that can affect the efficiency, one being sterics around the alkene. As substituents become larger and the number of substituents increase, we find a dramatic decrease in RCM yield. Here we report the effect that allylic substitutions have on the shape and topology, as well as the RCM yield of various [13]-macrodilactones.


Using Small-angle X-ray Scattering to Study the Alignment of Coil-Coil Block Copolymers with Magnetic Fields. Yekaterina Rokhlenko, Yale University.

Abstract: Magnetic field alignment of block copolymers (BCPs) has typically relied on the presence of liquid crystalline or crystalline assemblies to provide sufficient magnetic anisotropy to drive alignment. Recently we have shown that alignment is also possible in simple coil-coil BCPs. In particular, alignment of lamellae was observed in poly(styrene-b-4-vinylpyridine) (PS-b-P4VP) on cooling across the order-disorder transition (Todt) at field strengths as low as 2 T, with alignment improving markedly with increasing field strength and decreasing cooling rate. Here we discuss the intrinsic chain anisotropy which drives the observed alignment, and its display as a net microdomain anisotropy due to chain tethering at the block interface. We use in-situ X-ray scattering to study the phase behavior and temperature-, time-, and field- dependent dynamics of magnetic alignment in coil-coil BCPs, highlighting the important roles of chain anisotropy and grain size in alignment. For the right combination of field strength and grain size, we can leverage intrinsic chain anisotropy to magnetically direct self-assembly in other coil-coil systems, including cylinder-forming poly(styrene-b-dimethylsiloxane).


X-ray reflectivity of a highly ordered biofilm protein on mica. M. Daniela Morales Acosta, University of Connecticut.

Abstract: Biofilms are densely packed communities of microorganisms capable to protect growth of microbes. Biofilms contain proteins as one of the major constituents. Bacillus subtilis lipase LipA (BslA) protein possesses a remarkable hydrophobic "cap", which modify the physicochemical properties of surfaces and interfaces that, for example, may protect a bacteria colony from antimicrobial agents. The study of the molecular structure of biofilms is therefore essential to new strategies for designing antimicrobial agents and surface-active biofilms. In this study, we investigate the structure of a BslA film using x-ray reflectivity (XRR). Through the XRR analysis it was possible to identify the water-repellent cap and the head group of the colony biofilm and to determine with high precision their thickness and density. The total thickness and values of densities are consistent with the crystal structure of BslA at a full surface coverage. Our results confirm the formation of a densely packed structure (occupied area 24.7 x 24.7 Å2/molecule), and indicate that the BslA protein lies on the mica with its hydrophobic cap exposed to the environment, conferring the hydrophbic character to the biofilm.


Oligonuclear Pyridine Alkoxide Ligands: First-row Metal Clusters and High Oxidation State Promotion. Dimitar Shopov, Shashi Sinha, and Liam Sharninghausen, Yale University.

Abstract: Modification of the synthesis of our highly successful pyridine alkoxide ligand afforded methylene-bridged dimers and trimers, whose isomers were successfully separated. Unlike the original monomer, these ligands readily produced characterizable first-row metal clusters with manganese, copper, nickel, and cobalt, in some cases with two cis open sites suitable for catalysis. Also presented is a mononuclear iridium complex, the first known to incorporate four of the highly donor alkoxide groups. As a result, an Ir(IV) resting state and a reactive but metastable Ir(V) state are observed and crystallized. The latter is the first known example of an isolated Ir(V) complex without fluorides or organometallic ligands.