Systematic functionalization of a metal-organic framework via a postsynthetic modification approach

The pendant amino groups in isoreticular metal-organic framework-3 (IRMOF-3) were subjected to postsynthetic modification with 10 linear alkyl anhydrides (O(CO(CH2)nCH3)2 (where n = 1 to 18) and the extent of conversion, thermal and structural stability, and Brunauer-Emmett-Teller (BET) surface areas of the resulting materials were probed. (1)H NMR of digested samples showed that longer alkyl chain anhydrides resulted in lower conversions of IRMOF-3 to the corresponding amide framework (designated as IRMOF-3-AM2 to IRMOF-3-AM19). Percent conversions ranged from essentially quantitative (approximately 99%, -AM2) to approximately 7% (-AM19) with IRMOF-3 samples. Modified samples were thermally stable up to approximately 430 degrees C and remained crystalline based on powder X-ray diffraction (PXRD) measurements. Under specific reaction conditions, significant conversions were obtained with complete retention of crystallinity, as verified by single-crystal X-ray diffraction experiments. Single crystals of modified IRMOF-3 samples all showed that the F-centered cubic framework was preserved. All single crystals used for X-ray diffraction were analyzed by electrospray ionization mass spectrometry (ESI-MS) to confirm that these frameworks contained the modified 1,4-benzenedicarboxylate ligand. Single crystals of each modified IRMOF-3 were further characterized by measuring the dinitrogen gas sorption of each framework to determine the effects of modification on the porosity of the MOF. BET surface areas (m(2)/g) confirmed that all modified IRMOF-3 samples maintained microporosity regardless of the extent of modification. The surface area of modified MOFs was found to correlate to the size and number of substituents added to the framework.     

Chemical synthesis of a glycoprotein having an intact human complex-type sialyloligosaccharide under the Boc and Fmoc synthetic strategies

The chemical synthesis of complex glycoproteins is an ongoing challenge in protein chemistry. We have examined the synthesis of a single glycoform of monocyte chemotactic protein-3 (MCP-3), a CC-chemokine that consists of 76 amino acids and one N-glycosylation site. A three-segment native chemical ligation strategy was employed using unprotected peptides and glycopeptide. Importantly, the synthesis required the development of methods for the generation of sialylglycopeptide-alphathioesters. For the sialylglycopeptide-alphathioester segment, we examined and successfully implemented approaches using Fmoc-SPPS and Boc-SPPS. To avoid use of hydrogen fluoride, the Boc approach utilized minimal side chain protection and direct thiolysis of the resin bound peptide. Using these strategies, we successfully synthesized a glycoprotein having an intact and homogeneous complex-type sialyloligosaccharide.     

Syntheses and phosphorescent properties of blue emissive iridium complexes with tridentate pyrazolyl ligands

Novel neutral mixed-ligand Ir(N=C=N)(N=C)X complexes (N=C=N = 1,3-bis(3-methylpyrazolyl)benzene (bpzb), 1,5-dimethyl-2,4-bis(3-methylpyrazolyl)benzene (dmbpzb), and 1,5-difluoro-2,4-bis(3-methylpyrazolyl)benzene (dfbpzb); N=C = 2-phenyl pyridine (ppy); and X = Cl or CN) have been synthesized and characterized. An X-ray single-crystal structure of the complex Ir(dmbpzb)(ppy)Cl shows that the nitrogen atom in the ppy ligand occupied the trans position to the carbon atom in the tridentate N=C=N ligand of dmbpzb with the Ir-C bond length of 1.94(1) A, whereas the coordinating carbon atom occupied the trans position of chlorine. Electrochemical data show that the complexes exhibit an oxidation Ir(III/IV) process in the potential range of +0.5 approximately 0.9 V and two irreversible reductions at approximately -2.6 and -3.0 V against Fc (0)/Fc (+), respectively. All of the Ir(III) complexes do not emit phosphorescence at room temperature, although strong phosphorescence is exhibited at 77 K with the 0-0 transition centered at around 450 nm and lifetimes of 3-14 mus. DFT calculations indicate that the HOMOs are mainly localized on iridium 5dpi and chlorine ppi*, whereas the LUMOs are mainly from the ppy ligand pi* orbitals. The phosphorescence originates from a (3)LC state mixed with the (3)MLCT and (3)XLCT ones. Temperature-dependent lifetime measurements of Ir(dfbpzb)(ppy)Cl reveal the existence of a thermal deactivation process with a low activation energy (1720 cm (-1)) and very high frequency factor (2.3 x 10 (13) s (-1)). An unrestricted density functional theory indicates that the dd state, in which both the Ir-N (pyrazolyl) bond lengths increase considerably, exists almost at the same energy as that for the phosphorescent state. A thorough analysis based on the potential energy surfaces for the T 1 and S 0 states allows us to determine the reaction pathway responsible for this thermal deactivation. The calculated activation energies of 1600 approximately 1800 cm (-1) are in excellent agreement with the observed values.     

Formation of 1,4-diphosphinobenzenes via tele-substitution on fluorobenzenechromium complexes

The meta-tele-substitution of 2-(boranatophosphino)fluorobenzenechromium complexes took place with various lithiated secondary phosphine-boranes as nucleophiles to give para-substituted bis(boranatophosphino)benzenechromiums. It was revealed that the yield of the tele-substitution product was strongly affected by the strength of a proton acid. Isotope labeling experiments indicated that 1,5-hydrogen migration was involved in this transformation.     

Ti-mediated direct and highly stereoselective Mannich reactions between esters and oxime ethers

The first general method of direct and highly stereoselective Ti-mediated Mannich reaction between three types of simpleesters and E and Z mixtures of oxime ethers (aliphatic and aromatic) is accomplished.     

Radiation- and photo-induced activation of 5-fluorouracil prodrugs as a strategy for the selective treatment of solid tumors

5-Fluorouracil (5-FU) is used widely as an anticancer drug to treat solid cancers, such as colon, breast, rectal, and pancreatic cancers, although its clinical application is limited because 5-FU has gastrointestinal and hematological toxicity. Many groups are searching for prodrugs with functions that are tumor selective in their delivery and can be activated to improve the clinical utility of 5-FU as an important cancer chemotherapeutic agent. UV and ionizing radiation can cause chemical reactions in a localized area of the body, and these have been applied in the development of site-specific drug activation and sensitization. In this review, we describe recent progress in the development of novel 5-FU prodrugs that are activated site specifically by UV light and ionizing radiation in the tumor microenvironment. We also discuss the chemical mechanisms underlying this activation.     

Photoelectrochemical evaluation of pH effect on hole transport through triplex-forming DNA immobilized on a gold electrode

We characterized pH effect on hole transport through DNA duplexes possessing a partial triplex-forming region. Direct electrochemical measurement of the current response of photosensitizer-tethered DNA immobilized on a gold electrode revealed that the partial triplex formation under acidic conditions suppressed photocurrent due to hole transport, while dissociation of the triplex into the duplex as occurred upon increasing pH values recovered the photocurrent efficiency. Reversible conversion between duplex and triplex induced upon cyclic alternation of pH values resulted in a rise and fall of photocurrent responses, indicating that pH change may feature in the switching function of hole transport in DNA. These electrochemical behaviors could be correlated to the results obtained in long-range photo-oxidative DNA cleavage experiments, in which DNA cleavage at the hole trapping site beyond the triplex region was significantly suppressed under triplex-forming acidic conditions.     

Total synthesis of (+/-)-stemonamide and (+/-)-isostemonamide using a radical cascade

Total synthesis of stemonamide and isostemonamide is described. The concise construction of the tricyclic core of these alkaloids was achieved by radical cascade involving 7-endo and 5-endo cyclizations.     

Three new polyketide-terpenoid hybrids from Penicillium sp

Three novel hybrid polyketide-terpenoid metabolites were isolated from a Penicillium minioluteum strain. Their structures were determined by NMR spectroscopic analyses and X-ray crystallography. The proposed biosynthetic pathway including a unique retro-Claisen migration of methyl carbonate correlates the three compounds with berkeleydione and berkeleytrione.