The combination of inorganic porous silicon (pSi) and flexible biocompatible polymers has been shown to yield more beneficial hybrid scaffolds for tissue engineering (i.e. use of synthetic materials to facilitate healing). PSi has a variety of tunable properties, including pore size, pore volume and non-toxic degradation; the addition of a flexible polymer component provides the benefit that such a construct can easily conform to any shape of the actual site of an injury/disease, suggesting that pSi/polymer composites can be suitable candidates for localized drug delivery.
In this work, composite materials consisting of oxidized porous silicon (ox-pSi) with particle size of ~ 30 μm and pore size of 40-100 nm and thin polycaprolactone (PCL) films. PCL solid films were fabricated from an initial fibrous structure that was exposed to a temperature of 65-80 oC causing fusion of these fibers into a solid film. Ox-pSi particles were then physically embedded into PCL films, resulting in ~30-40% loading of ox-pSi (ox-pSi/PCL film). Ox-pSi particles of the composite were loaded with a model cytotoxic (anticancer) drug-camptothecin (CPT). Drug release from the ox-pSi particles alone and ox-pSi/PCL film composites was monitored fluorometrically, showing distinct release profiles for each material.
Ox-pSi/PCL film composites release a CPT payload in accordance with the Higuchi release model and showed a significant decrease in burst effect compared to ox-pSi particles only. In addition, composite evolution after 5 weeks in a given solution was examined by determining weight loss and surface morphology/composition (FESEM). Overall weight loss of the composites was less then 10% mainly attributed to pSi particles detachment and dissolution.

Iron plays a pivotal role in metabolism and transport processes in nature but can also be used to accomplish important chemical transformations on the bench top; recently, iron(II) salts have been shown to catalyze direct Suzuki – Miyaura coupling of N-heterocyclic compounds and arylboronic acid derivatives in the presence of oxygen. Presented herein are three tetra-aza macrocyclic iron(III) complexes [L1Fe(III)(Cl)2]+ (L1Fe), [L2Fe(III)(Cl)2]+ (L2Fe), and [L3Fe(III)(Cl)2]+ (L3Fe) [L1 (Pyclen)=1,4,7,10-tetra-aza-2,6-pyridinophane; L2 =3,6,9,15-tetraazabicyclo[9.3.1]penta-deca-1(15),11,13-trien-13-ol; L3 =3,6,9,15-tetra-azabicyclo[9.3.1]penta-deca-1(15),11,13-trien-12-ol] that catalyze the coupling of pyrrole and phenylboronic acid. Following the synthesis and reactivity studies, investigation into the oxidation state of the iron center throughout the catalytic cycle was explored. The results of this work to date will be presented and will facilitate the understanding of challenging chemical reactions catalyzed using inexpensive earth abundant metals such as iron.

Nanomaterials based on cerium (IV) oxide, CeO2, have been extensively investigated due to interesting chemistry from a readily available transition between Ce3+ and Ce4+. Oxygen vacancies present in the oxide lattice combined with the available redox transition gives CeO2 materials antioxidant and enzyme mimetic behavior. The addition of tri-valent, fluorescent ions such as Eu3+ further increase the oxygen vacancy concentration, may allow control over the Ce3+/Ce4+ ratio, and may add fluorescence to the doped material. These properties give europium doped cerium oxide (EuCeO¬2) potential applications within biological systems.
Eumelanin is a complex dark brown pigment originating from the oxidation and oligomerization of tyrosine. The pigment can also be synthesized through the auto-oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA). While its structure has not been fully determined, eumelanin has shown antioxidant and free-radical scavenging behavior, strong UV-VIS absorption, and conductive properties. The pigment has been researched for its radiation damage protection, and for activity against amyloids associated with Parkinson’s and Alzheimer’s disease.
Our research thus far has focused on the controlled synthesis of various EuCeO2 nanomaterials, and their interaction with the auto-oxidation of L-DOPA to eumelanin as measured through the observation of eumelanin fluorescence at 471 nm. Nanorods, nanowires, and nanocubes of EuCeO2 were each synthesized with a range of dimensions and europium content. EuCeO2 nanorods and nanocubes were synthesized through precipitation of EuCe(OH)3 and a subsequent hydrothermal reaction between 100°C and 180°C. Nanowires were synthesized using electrospinning and annealing techniques. All materials were analyzed using transmission electron microscopy (TEM), energy dispersive x-ray analysis (EDX), and powder x-ray diffraction (XRD).
The presence of CeO2 or EuCeO2 materials in L-DOPA containing solutions consistently suppressed the eumelanin-associated fluorescence intensity. Various parameters, including temperature, pH, nanomaterial concentration and morphology, and europium doping concentration have been evaluated for their potential impact on the evolution of eumelanin from L-DOPA in the presence of these EuCeO2 nanomaterials.

Monika Hailey
SRS 2017
Neilson Group
Synthesis of Silicon-Nitrogen Polymer Precursors
The Neilson research group focuses on developing synthetic routes to new organic-inorganic hybrid polymers. Specifically, one class of potential polymers contain silicon-nitrogen bonds, alternating with organic spacer groups along the polymer backbone. These two elements were chosen in order to obtain a system whose stability is similar to that of organic (carbon-based) polymers. Organic polymers are very stable and can be found in everyday life. In addition, silicon-oxygen polymers are used in several commercial applications. Silicon-nitrogen polymers could possibly serve as precursors to other new polymeric and/or solid state materials.
Experiments were conducted to produce a variety of small molecule precursors to the new silicon-nitrogen polymer system. Seven silicon-nitrogen small molecules were synthesized, in fairly good yield, and characterized using 1H NMR spectroscopy. When attempting to purify some of these small molecules, there was some thermal decomposition, possibly leading to the desired polymer. Future experiments will investigate the synthetic potential of these new compounds.

Molecularly imprinted polymers (MIPs) are advantageous to chemists both in their ability to drive the equilibrium of a reaction toward a desired product and in chromatography. In this project we focused on the use of MIPs in a chromatographic sense to selectively isolate menthyl-(hydroxymethyl)-phenyl phosphinate in the SP form from a mixture of both diastereoisomers. Both R and S configurations are made in equal proportions but the yield from isolation and crystallization of each pure diastereoisomer is low. Production of a polymer containing pockets specific to the configuration of one diastereoisomer enables an easier method to isolate one diastereoisomer through absorption by the polymer and subsequent release. The potential for MIPs for these P-stereogenic compounds lies in the increase yield of pure crystals and therefor decreased cost of production.

This project was aimed to prepare stable isosteric analogs of S-adenosylmethione (SAM) whose sulfur atom is replaced by a nitrogen atom and to evaluate these analogs for the SAM riboswitch-binding activities and antibacterial activities. In bacteria, SAM binds to the SAM riboswitch, which regulates the biosynthesis of methionine and cysteine, two amino acids essential for survival. Therefore, synthetic molecules that bind to SAM riboswitches have the potential to kill bacterial cells.
Three different classes of SAM riboswitches exist in bacteria (SAM I, II, and III). Each class of SAM riboswitch gene under control of T7 promoter was prepared by the overlapping extension polymerase chain reaction of synthetic oligonucleotides. Each SAM riboswitch gene was successfully cloned into the pUC19 plasmid and verified by DNA sequencing. A high concentration of each SAM riboswitch DNA was prepared by PCR and further converted to the corresponding SAM riboswitch RNA molecules by in vitro transcription using T7 RNA polymerase. All three classes of SAM riboswitches will be tested for binding to the synthesized SAM analogs.

Plant based nanotechnology for drug delivery and anti-inflammatory therapy
Jhansi Kalluri, Julianna West, Giridhar Akkaraju, Leigh Canhm and Jeffery L. Coffer*
Abstract:
Chronic inflammation is one of the characteristics of Alzheimer’s, cancer, and selected auto inflammatory diseases. Medicinal plant extracts rich in polyphenols have shown the ability to aid in the prevention of degenerative diseases such as Alzheimer’s due to their anti-inflammatory and anti-oxidant properties. One of the problems of using polyphenols to treat these diseases is their potentially low bioavailability and short half-life in vivo. An alternative to using free compound is to use plant polyphenol-loaded nano/micro particles to increase their bioavailability and half-life.
Equisetum arvense is a silicon accumulator plant serving as a source for a viable eco-friendly route for fabricating nanostructured porous silicon (pSi) drug delivery carriers; at the same time, if selected plant components contain medicinally-active species as well, then the single substance can provide not only the nanoscale high surface area drug delivery carrier (pSi), but the drug itself. With this idea in mind, porous silicon was fabricated from stems/fronds of the silicon accumulator plant Equisetum arvense and the anti-inflammatory activity of the leaf components (aqueous ethanol extract) of Equisetum arvense was tested using a luciferase assay. We evaluated the dose dependent activity of the extract to inhibit TNF-induced NF- kB activation. Our long-term goal is to measure the anti-inflammatory activity of extract-loaded porous silicon particles in a sustained manner.

Semiconducting silicon (Si) is a promising element that has been extensively studied in various fields ranging from microelectronics to bio-relevant applications.1 In fact, nanostructured porous silicon has received widespread attention due to its unique chemical and physical characteristics.1 Another relatively more well-defined example of nanostructured silicon is Si nanotubes (SiNTs) with well-characterized sidewalls, inner void space and lengths, allowing opportunities to study its potential properties in diverse fields, such as Li ion batteries, solar cells.2,3 In particular, SiNTs are potential vectors in drug delivery systems. The available interior free space of the NTs offer the material the ability of confining a desired amount of payload of therapeutic agents. Moreover, the available silanol groups on the surface of the NTs also enable attachment to a linker, whose other end is subsequently attached to a drug molecule of interests. Within a biological environment, therapeutic molecules of interest can be released in a sustained manner into targeted sites through either dissolution of the SiNT carriers or their detachment from the linkers.
In terms of therapeutic candidates, cisplatin has been renowned for its ability to treat a variety of cancers including lymphomas, carcinomas, etc. Due to low chloride ions concentrations (4-12mM) in the intracellular environment of cancer cells, chloride ligands on cisplatin are readily displaced by water, producing either cis-[PtCl(NH3)2(H2O)]+ or cis-[Pt(NH3)2(H2O)2]2+ aquo complexes, which actively target DNA and trigger apoptosis.4 However, since drug resistance is developed in cancer cells and undesirable interactions between cisplatin and other biological molecules occur, the therapeutic effects become diminished and negative side effects are also observed.5,6 In order to enhance the therapeutic efficiency of cisplatin, in this project, SiNTs are employed as carriers that can be loaded with cisplatin and potentially deliver the drugs to the desired sites. For the purpose of controlling the release of cisplatin from SiNTs, 3-aminopropyltriethoxysilane (APTES) is employed as the linker, which can covalently bind to the nanotubes through the available silanol groups on the surface, and the amino group on the other end of APTES can subsequently coordinate cisplatin.
In this study, SiNTs with lengths less than 1 µm are used (for optimal cellular uptake), and a sidewall thickness ~ 10 nm for desirable dissolution within a biological environment. Moreover, the distinct porous morphology of the nanotubes permits infiltration of the molecules of interest. By varying solvents (acetone and toluene) of APTES solution and functionalization time, the amount of cisplatin loaded into SiNTs can be modulated ranging from 20-40 weight %, thereby suggesting the ability of SiNTs to carry therapeutic agents.
References
1. Canham, L.T. Hanbook of Porous Silicon. Switzerland: Springer International Publishing AG, 2014.
2. Tesfaye A, Gonzalez R., Coffer J., Djenizian T. Porous Silicon Nanotube Arrays as Anode Material for Li-Ion Batteries, ACS Appl Mater. Inter. 2015, 7, 20495−20498.
3. Gonzalez-Rodriguez R., Arad-Vosk N., Rozenfeld N, Sa’ar A, Coffer JL (2016) Control of CH3NH3 PbI3 Perovskite Nanostructure Formation through the Use of Silicon Nanotube Templates, Small 2016, 12, 4477–4480.
4. Ma P., Xiao H., Li C., Dai Y., Cheng Z., Hou Z., Lin J. Inorganic nanocarriers for platinum drug delivery, Materials Today 2015, 18(10), 554-564.
5. Martin L.P., Hamilton T.C., Schilder R.J. Platinum Resistance: The Role of DNA Repair Pathways, Clin Cancer Res. 2008, 14(5):1291-1295.
6. Xue X., You S., Zhang Q., Wu Y., Zou G., Wang P. C., Zhao Y., Xu Y., Jia L., Zhang X., Liang X. Mitaplatin Increases Sensitivity of Tumor Cells to Cisplatin by Inducing Mitochondrial Dysfunction, Mol. Pharmaceutics, 2012, 9 (3), 634–644.

Various total syntheses of the Lycorine-type pharmacologically active alkaloids hippadine and pratosine have been developed. However, most of these synthetic routes require prohibitively expensive materials and/or achieve yields that are subpar, making these schemes unlikely to be used in an industrial setting. Current research involves developing better synthetic methods for these two alkaloids starting with a 6,7-disubstituted isoquinoline. These syntheses are appealing since they utilize readily available starting materials and avoid expensive catalysts. The key step in the synthetic scheme centers around an intramolecular de Mayo photocyclization which involves a reaction between an alkene moiety in the isocarbostyril system and a 1,3-diketone (a functionalized tether on nitrogen), which forms a third ring in the structure of the molecule. Research on a model system (an isocarbostyril without the substituents at positions 6 and 7) for these natural products has been done in order to elucidate the optimal conditions for each step on the synthetic strategy. Initial attempts were made in order to synthesize the 6,7-disubstituted isocarbostyril with the 1,3-diketone tether so that the deMayo photocyclization could be performed. However, the established synthetic strategy led to compounds along the synthetic route that had very undesirable solubility properties. To resolve this issue, the substituents were replaced with bulkier, more non-polar moieties in order to increase the solubility of the compound in ethyl ether.

Traditionally the genetic code has utilized the canonical twenty amino acids in order to construct proteins and facilitate life. The process of translation involves an RNA template and codons that will be read and matched to corresponding tRNA molecules carrying charged amino acids. An aminoacyl tRNA synthetase specific to each amino acid is responsible for loading and charging the amino acid to the tRNA. In recent years, a few orthogonal pairs of the tRNA and aminoacyl tRNA synthetase have been utilized to expand the genetic code past the traditional 20 amino acids. Expanding the genetic code allows for new insight into protein function, structure, and interactions within the cell. The introduction of new amino acids could lead to proteins with new chemical or biological activity and even advantageously alter function leading to evolutionary events. In our research we attempt to incorporate unnatural amino acids using a leucyl-tRNA synthetase from Methanobacterium thermoautotrophicum and a tRNA which will suppress the amber stop codon (TAG). A mutant LeuRS lacking an editing domain (MLRS CP1) was generated. The best mutant was isolated and sequenced. The leucine binding site, determined from sequence homology, was randomized at five amino acids to create a library of mutants. The best mutant is selected through a positive selection process where only MLRS CP1 that add an amino acid to the tRNA will survive in the presence of chloramphenicol. Finally, in a negative selection step, those mutants which add natural amino acids to the tRNA will die in the presence of 5-fluorouracil. The library can then be used for further experiments to determine how effectively unnatural amino acids are incorporated.