Zwitterionic materials are useful tools in material science and biology as they provide high water solubility while preventing non-specific interactions. Quantum dots (QDs) functionalized with zwitterionic and quaternary ammonium ligands were synthesized to investigate their interactions with the outer membrane of HeLa cells. Quaternary ammonium functionalized quantum dots adhered strongly to the cell surface while zwitterionic QDs had no cell adhesion. These results demonstrate that future non-interacting nanoparticles based on this design are possible.

A series of novel β,γ-methylene-, monofluoromethylene-, and difluoromethylene-bisphosphonophosphate alkyl monoesters was synthesized. The compounds were conveniently detected during preparative HPLC using post-column derivatization with a phosphate-specific chemosensor.

Progress in the synthesis of novel fluorescent conjugates of N-heterocyclic bisphosphonate drugs and related analogues, together with some recent applications of these compounds as imaging probes, are briefly discussed.

A green, straightforward and novel method for oxidation of thiols to the corresponding disulfides is reported using K(2)S(2)O(8) in the ionic liquid 1-butyl-3-methylimidazolium bromide [(bmim)Br] at 65-70 °C. The corresponding disulfides were obtained in excellent yield and short reaction time.

Elemental selenium generated by the photobleaching of selenomerocyanine dyes forms conjugates with serum albumin and serum lipoproteins that are toxic to leukemia and selected solid tumor cells but well tolerated by normal CD34-positive hematopoietic stem and progenitor cells. Serum albumin and lipoproteins act as Trojan horses that deliver the cytotoxic entity (elemental selenium) to tumor cells as part of a physiological process. They exploit the fact that many tumors have an increased demand for albumin and/or low-density lipoprotein. Se(0)-protein conjugates are more toxic than selenium dioxide, sodium selenite, selenomethionine, or selenocystine. They are only minimally affected by drug resistance mechanism, and they potentiate the cytotoxic effect of ionizing radiation and several standard chemotherapeutic agents. The cytotoxic mechanism of Se(0)-protein conjugates is not yet fully understood. Currently available data are consistent with the notion that Se(0)-protein conjugates act as air oxidation catalysts that cause a rapid depletion of intracellular glutathione and induce apoptosis. Drugs modeled after our Se(0)-protein conjugates may prove useful for the local and/or systemic therapy of cancer.

Synthetic approaches to a new class of tyrosine-linked prodrugs of two 3-hydroxy-2-(phosphonomethoxypropyl) (HPMP) nucleotide analogues ((S)-HPMPC and (S)-HPMPA) are outlined.

A new reaction of elemental phosphorus (P) with elemental sulfur and 1,3-propylene glycol in the presence of different amines has been investigated. Ammonium salts of O,O'- alkylenedithiophosphoric acids have been observed as main products of the reaction. Octathiotetraphosphetane ammonium salts were formed as minor products. The reaction is characterized by a complete conversion of white phosphorus and is not accompanied by the release of hydrogen sulfide. The crystal structure features's of diethylammonium salt of O,O'-propylenedithiophosphoric acid were determined using single crystal X-ray diffraction. Piperidinium salt of octathiotetraphosphetane in DMSO and DMF solutions possess significant antifungal activity against Candida albicans.

Individual diastereomers of CXY bisphosphonate analogues of dNTPs or NTPs are useful chemical stereoprobes to investigate interactions within the chiral active site environment of enzymes such as polymerases and kinases. We previously reported synthetic access to β,γ-CHX-dGTPs (X = F or Cl) via a bisphosphonate synthon with an (R)-methyl mandelate auxiliary and have extended this approach to dTTP and dATP analogues. As removal of the chiral auxiliary by (Pd/C) hydrogenolysis is incompatible with the cytosine heterocycle and also with X = Br, we have now designed bisphosphonate synthons using (R)-(+)-α-ethylbenzylamine or methyl (R)-(-)-phenylglycine auxiliaries and equipped with an o-nitrobenzyl ester protecting group allowing photochemical deprotection. These new synthons have made possible the first syntheses of individual dCTP and monobromo-substituted dNTP β,γ-CHX diastereomers.

During the course of an investigation of targeted inhibition of DNA polymerase beta (pol β) lyase activity using small molecules, we observed the formation of an aldimine between (2-formyl)phenylphosphonic acid (2FPP) and butylamine under basic aqueous conditions; complete deprotonation of the phosphonate group was required to stabilize the imine product. Results of computational docking studies suggested that the reaction of Lys-72 on the lyase active site with an aldehyde group could be facilitated by a proximal phosphonate, not only because of the phosphonate's ability to mimic phosphate interacting with the DNA binding site, but also because of its ability to shield the imine against hydrolysis. Novel pol β lyase inhibitors were thus prepared using a 2FPP analogue with an amine linker; P-C bond formation in synthesis of this intermediate was possible with an unprotected aldehyde using palladium-catalyzed, microwave-assisted Michaelis-Arbuzov chemistry. These compounds, and structurally related derivatives lacking the aldehyde or phosphonate, were evaluated in an assay for pol β, to assess their potential for inhibition of pol β.

This paper describes the synthesis of several halogenated S and Se heterocycles and tests their biological activity by measuring the effects on the myeloid leukemia cell line, PLB-985 cells. We report that select compounds exhibit significant increases in mitochondria membrane potential and increased oxidative stress in PLB-985 cells. Our results contribute to the foundational knowledge of different S and Se containing compounds and their possible impacts on human cells.