Two new rhodium-substituted polyoxoniobates, [H2RhNb9O28](6-) (RhNb9) and [Rh2(OH)4Nb10O30](8-) (Rh2Nb10) are reported. The two distinct Rh(III)-substituted niobate clusters behave differently when the pH is raised with TMAOH: the Rh2Nb10 is stable until pH ∼ 12.7, but RhNb9 dissociates to form RhNb5 and RhNb10, similar to some of our other metal-substituted niobates, such as the MNb9 ions (M = Cr or Mn), which transform to MNb10 when the solution pH is raised.

Two new substituted polyoxotantalate clusters, [Ti2 Ta8 O28 ](8-) and [Ti12 Ta6 O44 ](10-) , considerably expand the pH range where tantalates persist in aqueous solution. The structures of [Ti2 Ta8 O28 ](8-) and [Ti12 Ta6 O44 ](10-) are reported as tetramethylammonium salts after synthesis at hydrothermal conditions in aqueous solution. These Ti-substituted polyoxotantalate clusters have analogues among recently discovered niobates, but are slightly larger and more persistent in solution. Most importantly, they exhibit a much wider range of pH stability than the familiar hexatantalate cluster, which is the only other tantalate known to be stable at highly basic pH conditions. These molecules are kinetically stable to near-neutral pH, making them excellent synthons for further development into materials and catalysts, and an significant advance in adapting tantalates for use in aqueous solutions.

Polyoxoniobate clusters that are stable in acidic solutions are rare and particularly useful in industrial processes. Here we report a new pentaphosphate niobate polyoxometalate cluster (TMA)9H3Nb9P5O41·28H2O (Nb9P5) that is stable over a wide pH range and that can be converted reversibly into the peroxo form.

Caps in α-Keggin-type polyoxometalates [PM2Nb12O40](9-) (M: Nb[double bond, length as m-dash]O or V[double bond, length as m-dash]O) can be removed in basic condition to produce uncapped [PNb12O40](15-). Transmetalation or capping occurs from the reaction of [PNb14O42](9-) or [PNb12O40](15-) with either Sb2O3 or V2O5 to form [PSb2Nb12O40](9-) or [PV2Nb12O42](9-), respectively.

Two new peroxoniobophosphate clusters were isolated as tetramethylammonium (TMA) salts having the stoichiometries: TMA5[HNb4P2O14(O2)4]⋅9 H2O and TMA3[H7Nb6P4O24(O2)6]⋅7 H2O. The former is stable over the pH range: 3

In prior studies, aqueous Hf sulfate-peroxide solutions were spin-coated, dehydrated, patterned by electron-beam lithography, ion-exchanged (OH(-) for SO4(2-)), and finally converted to HfO2 hard masks via annealing. The atomic-level details of the underlying aqueous chemistries of these processes are complex and yet to be understood. Yet a thorough understanding of this specific chemical system will inspire development of design rules for other aqueous-precursor-to-solid-state metal oxide systems. Often-observed crystallization of the Hf18 polyoxometalate from aqueous Hf sulfate-peroxide precursor solutions has led us to believe that Hf18 may represent an important intermediate step in this process. However, via detailed solution studies described here (small-angle X-ray scattering, electrospray ionization mass spectrometry, and Raman spectroscopy), we ascertained that Hf18 is in fact not a prenucleation cluster of Hf sulfate coatings. Rather, the Hf tetramers, pentamers, and hexamers that are the core building blocks of Hf18 are robustly persistent over variable compositions and aging time of precursor solutions, and therefore they are likely the rudimentary building blocks of the deposited thin-film materials. These Hf clusters are capped and linked by sulfate and peroxide anions in solution, which probably prevents crystallization of Hf18 during the rapid dehydration process of spin-coating. In fact, crystallization of Hf18 from the amorphous gel coating would be detrimental to formation of a high-density conformal coating that we obtain from precursor solutions. Therefore, this study revealed that the well-known Hf18 polyoxometalate is not likely to be an important intermediate in the thin-film process. However, its subunits are, confirming the universal importance of deriving information from the solid state, albeit judiciously and critically, to understand the solution state.

The discovery of a new variation on the Davis-Beirut reaction is described in which an atypical heterocyclic framework (the anthranil or benzo[c]isoxazole framework) is formed as the result of diversion of a key reactive intermediate away from its expected reactivity-a potentially general approach to reaction design and development. Experimental and computational support for the proposed mechanism and origins of altered reactivity are described.

We previously identified a spiro [piperidine-4,1-pyrido [3,4-b]indole] class of co-potentiators that function in synergy with existing CFTR potentiators such as VX-770 or GLGP1837 to restore channel activity of a defined subset of minimal function cystic fibrosis transmembrane conductance regulator (CFTR) mutants. Here, structure-activity studies were conducted to improve their potency over the previously identified compound, 20 (originally termed CP-A01). Targeted synthesis of 37 spiro [piperidine-4,1-pyrido [3,4-b]indoles] was generally accomplished using versatile two or three step reaction protocols with each step having high efficiency. Structure-activity relationship studies established that analog 2i, with 6'-methoxyindole and 2,4,5-trifluorobenzyl substituents, had the greatest potency for activation of N1303K-CFTR, with EC₅₀ ∼600 nM representing an ∼17-fold improvement over the original compound identified in a small molecule screen.

The Cadogan cyclization is a robust but harsh method for the synthesis of 2 H-indazoles, a valuable class of nitrogen heterocycles. Although nitrene generation by exhaustive deoxygenation is widely accepted as the operating mechanism in the reductive cyclization of nitroaromatics, non-nitrene pathways have only been theorized previously. Here, 2 H-indazole N-oxides were synthesized through an interrupted Cadogan/Davis-Beirut reaction and are presented as direct evidence of competent oxygenated intermediates; mechanistic implications for both reactions are discussed. Isolation and characterization of these N-oxides enabled a formal Cadogan cyclization at room temperature for 2 H-indazole synthesis.

We previously identified phenylquinoxalinone CFTR_act-J027 (4) as a cystic fibrosis transmembrane conductance regulator (CFTR) activator with an EC₅₀ of ∼200 nM and demonstrated its therapeutic efficacy in mouse models of constipation. Here, structure-activity studies were done on 36 synthesized phenylquinoxalinone analogs to identify compounds with improved potency and altered metabolic stability. Synthesis of the phenylquinoxalinone core was generally accomplished by condensation of 1,2-phenylenediamines with substituted phenyloxoacetates. Structure-activity studies established, among other features, the privileged nature of a properly positioned nitro moiety on the 3-aryl group. Synthesized analogs showed improved CFTR activation potency compared to 4 with EC₅₀ down to 21 nM and with greater metabolic stability. CFTR activators have potential therapeutic indications in constipation, dry eye, cholestatic liver diseases, and inflammatory lung disorders.