Trinitromethane Research Articles

Detection of photoreversibility of NO<sub>2</sub>–ONO linkage isomerization in [Co(NH<sub>3</sub>)<sub>5</sub>NO<sub>2</sub>]Cl(NO<sub>3</sub> crystals by the photomechanical response method

Linkage isomerization NO2-ONO (nitro-nitrito) in the complex cation [Co(NH3)5NO2]2+ is a well-studied classical reaction. It is believed that the photoisomerization of the nitro form to nitrito in the crystalline phase achieves complete transformation at low temperature, while the reverse transformation proceeds as a first-order thermal intramolecular reaction upon heating of the crystals. To date, there is no information about the possibility of reverse photoisomerization. In this work, photoisomerization in [Co(NH3)5NO2]Cl(NO3) crystals is investigated by the analysis of crystal deformation caused by the transformation at different wavelengths. A change in the lattice parameters during the transformation leads to reliably measurable elongation and bending of acicular crystals. It is shown that the limiting elongation of the crystal under prolonged irradiation depends on the wavelength, which proves the reversibility of photoisomerization. The quantum yield of the reverse reaction is estimated to be 0.04 of the quantum yield of the direct reaction.

Synthesis of a new bifunctional NODA for bioconjugation with PSMA ligand and one-step Al18F labeling

The Al18F labeling method is a relatively new approach that allows radiofluorination of biomolecules such as peptides and proteins in a one-step procedure and in an aqueous solution. However, instability of the complex of [AlF]2+ with hexadentate chelator NOTA may attribute to the disassociation of free 18F− and [Al18F]2+ and accumulation in bone. In this study, we designed and synthesized a new bifunctional pentadentate AlF-chelator p-SCN-PhPr-NODA as well as its nitro form p-NO2-PhPr-NODA. Chelator p-NO2-PhPr-NODA exhibited increased Al (III) complexation kinetics determined by AA III complexation kinetic studies and stronger coordination ability towards [AlF]2+ according to DFT calculation studies in comparison with hexadentate chelator NOTA. As a proof of concept, bifunctional chelator p-SCN-PhPr-NODA was furthermore conjugated to a PSMA targeting moiety Glu-urea-Lys to form NODA-PrPh-GuL. The conjugated peptide showed acceptable radiochemical yield (12.5–16.4%) and efficiency with an excellent radiochemical purity (∼100% after SPE purification) in Al18F labeling. The labeled peptide exhibited good in vitro stability and significant specificity for PSMA. Biodistribution study and MicroPET scan in healthy Kun Ming mice with the labeled peptide were performed and demonstrated excellent in vivo stability of Al18F-labeled construct. In general, the successful application of the new bifunctional chelator in labeling dipeptide Glu-urea-Lys with Al18F could facilitate its possibility in conjugating with other peptides for PET imaging with enhanced in vivo stability, thus providing better in vivo performances.

Nitrated Fluorophore Formation upon Two-Photon Excitation of an Azide with Extended Conjugation

The transformation of an aromatic azide into a highly fluorescent species through a nonlinear optical process was studied. The azide system was designed to undergo N2 release and nitrene to nitro conversion upon two-photon electronic excitation. The formation of the nitro form of the compound through reactions with O2 and its high radiative quantum yield implies that the azide can be used as a biphotonic activatable fluorogen. The electronic state in which the azide to nitrene transformation takes place can be accessed nonlinearly with near-infrared light which allows for photoactivation with commonly available lasers. Furthermore, the system was built with a sulfonate functionality which allows for the molecule to be adsorbed at surfaces like that of cadmium sulfide nanocrystals which further improves the nonlinear optical absorption properties in the composite, through an energy transfer mechanism. The yield of the process as a function of the excitation photon energy together with computational studies indicate that the N2 release in this azide is due to a reactive channel in the second singlet excited state of the molecule. This feature implies that the system is intrinsically photostable for excitation below and above a certain wavelength and that the system can be phototriggered selectively by the nonlinear optical process.

New Synthetic Route of Nitroform (NF) from Acetylacetone and Study of the Reaction Mechanism

A new synthetic route of nitroform (NF), the crucial raw material of hydrazinium nitroformate (HNF), was presented in this paper. Preparation of NF with a series of α-methyl carbonyl compounds as substrates was investigated by utilizing fuming HNO3 (98%, white) as the nitrating system. The results indicated that acetylacetone showed a good efficiency for the further studied reaction. The influence of various factors, such as additives, reaction temperature, time, and the molar ratio of fuming nitric acid to acetic anhydride, on the yield of the NF was demonstrated. NF was obtained under optimized conditions with a good yield of 40.8%. The reaction mechanism, which involved nitration–hydrolysis–nitration–hydrolysis, was proposed and verified by the 13C NMR tracking. Acetylacetone displays excellent prospects for industrial production of NF, because of the use of inexpensive raw materials, mild conditions, and a satisfactory yield of NF.

A novel synthesis of nitroform by the nitrolysis of cucurbituril

Cucurbituril has a high symmetry and rigid structure. When cucurbit[6]uril (CB[6]) was nitrolyzed with the mixed solution of acetic anhydride in fuming nitric acid, nitroform (NF) was generated. NF also can be obtained by the nitration of both CB[5,7,8]. This nitration procedure provides a lower risk, inexpensive, new preparation of nitroform, and the reaction condition of this new method is very mild.

Studies on Synthetic Technology and Reduced Sensitivity Technology of Hydrazinium Nitroformate

A practical synthetic route of hydrazinium nitroformate (HNF) was reported in this paper. The preparation of intermediate nitroform (NF) from isopropyl alcohol was investigated by utilizing anhydrous nitric acid (HNO3) as a nitrating system. The influence of various factors such as reaction temperature, time, and amount of anhydrous HNO3 on yield of NF, as well as the effect of temperature on the extraction efficiency was demonstrated. NF was obtained with an optimal yield of 53.6%, far beyond that reported in the literature (25%). The synthesis of HNF was followed by the neutralization reaction of NF with equal molar hydrazine hydrate (80%) instead of hydrazine anhydrous. With the purpose of decreasing the sensitivity, the crystal morphology of HNF was adjusted through varied crystallization methods such as antisolvent crystallization, sono-crystallization and sequential cooling crystallization. HNF crystals obtained from sequential cooling crystallization displayed excellent morphology with a length/dia...

Photo-induced intramolecular hydrogen transfer in ortho-nitroaniline: A matrix-isolation infrared spectroscopic and quantum-chemical study

The photo-induced intramolecular hydrogen transfer in ortho-nitroaniline (ortho-NA) was investigated by matrix isolation infrared spectroscopy and quantum chemical calculations. Under UV irradiation of ortho-NA in solid argon, the hydrogen atom transferred isomer was formed. It was found that the isomer is stable and not rearranged to its nitro form upon diffusion annealing at 30K. The infrared spectra and vibrational frequency assignments of the newly observed isomer were reported, which were supported by quantum chemical calculations.

Photoactivated linkage isomerism in single crystals of nickel, palladium and platinum di-nitro complexes – a photocrystallographic investigation

Low temperature, single crystal photocrystallographic studies have been carried out on four square planar Group 10 complexes [Ni(PEt(3))(2)(NO(2))(2)] 1, [Pd(PPh(3))(2)(NO(2))(2)] 2, [Pd(AsPh(3))(2)(NO(2))(2)] 3 and [Pt(PPh(3))(2)(NO(2))(2)] 4, in which the two nitro groups adopt the trans configuration. Irradiation with UV light, at 100 K, of single crystals of complexes 1-3 photoisomerise from the η(1)-NO(2) nitro form to the η(1)-ONO nitrito form occurred. Complex 1 underwent 25% conversion to the nitrito form before crystal decomposition occurred. 2 and 3 underwent 46% and 39% conversion, respectively, to the nitrito form when a photostationary state was reached. While under the same experimental conditions 4 showed no isomerisation. The photocrystallographic results can be correlated with the results of DFT calculations and with the observed trends in the solution UV/visible absorption spectroscopy obtained for these complexes. The results suggest that while steric factors in the isomerization processes are important there may also be a kinetic effect relating to the lability of the metal involved.

Preparation and Antitumour Properties of the Enantiomers of a Hypoxia‐Selective Nitro Analogue of the Duocarmycins

Racemic 2-{[1-(chloromethyl)-5-nitro-3-{5-[2-(dimethylamino)ethoxy]indol-2-carbonyl}-1,2-dihydro-3H-benzo[e]indol-7-yl]sulfonyl}aminoethyl dihydrogen phosphate, a synthetic nitro derivative of the duocarmycins, is a hypoxia-selective prodrug active against radiation-resistant tumour cells at nontoxic doses in mice. An intermediate in the synthesis of this prodrug was resolved by chiral HPLC and the absolute configuration assigned by X-ray crystallography. The intermediate was used to prepare the prodrug's enantiomers, and also the enantiomers of the active nitro and amino metabolites. In vitro analysis in the human cervical carcinoma cell line SiHa showed that both nitro enantiomers are hypoxia-selective cytotoxins, but the "natural" S enantiomer is at least 20-fold more potent. Examination of extracellular amino metabolite concentrations demonstrated no enantioselectivity in the hypoxia-selective reduction of nitro to amino. Low levels of amino derivative were also found in aerobic cell suspensions, sufficient to account for the observed oxic toxicity of the nitro form. At an equimolar dose in SiHa-tumour bearing animals, the (-)-R enantiomer of the prodrug was inactive, while the (+)-S enantiomer caused significantly more hypoxic tumour cell kill than the racemate. At this dose, the combination of (+)-S-prodrug and radiation eliminated detectable colony-forming cells in four out of five treated tumour-bearing animals.

Nitrogen Release from Slow‐Release Fertilizers as Affected by Soil Type and Temperature

Loss of N from fertilized agricultural soils is a serious problem that can negatively affect environmental quality. Nitrogen loss can be moderated by using slow‐release fertilizer (SRF) products (e.g., those created through condensation of urea and formaldehyde) in place of 100% water‐soluble N. Release of N from SRFs is affected by the soil environment. To evaluate soil effects on N release, we conducted an incubation study in which temperature and soil type were varied. Four SRFs were studied: liquid Nitamin 30L (L30), liquid Nitamin RUAG 521G30 (G30), granular Nitamin 42G (N42) (all from Georgia Pacific Chemicals, Decatur, GA), and granular Nitroform (NF) (Agrium Advanced Technologies, Loveland, CO). The fertilizers were incubated for 78 d at 20, 25, and 30°C in a sandy soil and at 25°C in a loamy soil. Differential N release kinetics of the N sources were determined by measuring NH4–N and NO3–N concentrations throughout the incubation. Net N released as a percentage of total N in the fertilizer was significantly affected by N source, temperature, time, and soil type. Increasing temperature increased net N release. The N release rate decreased in the order N42 > G30 > L30 > NF in the sandy soil and G30 > N42 > L30 > NF in the loamy soil. Overall, the release rates of these fertilizers were greater in the loamy soil. The N release characteristics determined in this study can help in the selection of the appropriate SRF source for crops grown under different soil and climatic conditions to improve N use efficiency and minimize N loss to the environment.

Surface-Enhanced Infrared Absorption Spectroscopic Studies of Adsorbed Nitrate, Nitric Oxide, and Related Compounds. 3. Formation and Reduction of Adsorbed Nitrite at a Platinum Electrode

The formation, potential-dependent structural change, and reduction of adsorbed nitrite at a platinum electrode were examined in 0.1 M HClO4 and 0.1 M NaClO4 by surface-enhanced infrared absorption spectroscopy (SEIRAS). The band assigned to the symmetric NO2 stretch of the nitro form of nitrite appeared at around 1300 cm−1 in both solutions. The potential dependence of the spectra revealed that this adsorbed nitrite is converted to NO adsorbed at on-top, bridge, and defect sites via IR-inactive surface nitrite species. In 0.1 M HClO4, these three adsorbed NO species were also formed during the adsorption process from the solution NO formed by the disproportionation of nitrite. In addition to the reduction via the IR-inactive surface nitrite species, a direct conversion from adsorbed nitrite to adsorbed NO was also suggested in 0.1 M HClO4.

The Distal Pocket Histidine Residue in Horse Heart Myoglobin Directs the O-Binding Mode of Nitrite to the Heme Iron

It is now well-established that mammalian heme proteins are reactive with various nitrogen oxide species and that these reactions may play significant roles in mammalian physiology. For example, the ferrous heme protein myoglobin (Mb) has been shown to reduce nitrite (NO(2)(-)) to nitric oxide (NO) under hypoxic conditions. We demonstrate here that the distal pocket histidine residue (His64) of horse heart metMb(III) (i.e., ferric Mb(III)) has marked effects on the mode of nitrite ion coordination to the iron center. X-ray crystal structures were determined for the mutant proteins metMb(III) H64V (2.0 A resolution) and its nitrite ion adduct metMb(III) H64V-nitrite (1.95 A resolution), and metMb(III) H64V/V67R (1.9 A resolution) and its nitrite ion adduct metMb(III) H64V/V67R-nitrite (2.0 A resolution). These are compared to the known structures of wild-type (wt) hh metMb(III) and its nitrite ion adduct hh metMb(III)-nitrite, which binds NO(2)(-) via an O-atom in a trans-FeONO configuration. Unlike wt metMb(III), no axial H(2)O is evident in either of the metMb(III) mutant structures. In the ferric H64V-nitrite structure, replacement of the distal His residue with Val alters the binding mode of nitrite from the nitrito (O-binding) form in the wild-type protein to a weakly bound nitro (N-binding) form. Reintroducing a H-bonding residue in the H64V/V67R double mutant restores the O-binding mode of nitrite. We have also examined the effects of these mutations on reactivities of the metMb(III)s with cysteine as a reducing agent and of the (ferrous) Mb(II)s with nitrite ion under anaerobic conditions. The Mb(II)s were generated by reduction of the Mb(III) precursors in a second-order reaction with cysteine, the rate constants for this step following the order H64V/V67R > H64V >> wt. The rate constants for the oxidation of the Mb(II)s by nitrite (giving NO as the other product) follow the order wt > H64V/V67R >> H64V and suggest a significant role of the distal pocket H-bonding residue in nitrite reduction.

Correlations for photocatalytic activity and spectral features of the absorption band edge of TiO2 modified by thiourea

Doping of nanocrystalline TiO2 powders with sizes ranging from 9.5nm up to 19.1nm was carried out with thiourea (TU) to introduce the C, N and S-species into the TiO2. The crystal size was determined by X-ray diffraction. Doped-TiO2 particles were colored while the undoped TiO2 was white. The edge of the absorption band edge was analyzed to describe the TiO2 band gap according to the indirect transitions theory of semiconductors. In the former analysis the energy distribution of the doped centers is discussed in terms of the Urbach's tail theory (K=K0expσ((hν−Eg)/kT)), being K the absorbance in the Kubelka–Munk equation. Evidence is presented for thiourea doped-TiO2 leading to Urbach's tail associated with the formation of states in the band-gap rather than a narrowing of the band gap. The photocatalytic activity of the doped-TiO2 was tested by the reduction of tetra-nitromethane to nitroform and by the oxidation of I− to I3−. The rate of formation of nitroform (NF) produced under 460nm light increased for the smaller TiO2 nanoparticles. This suggests the formation of localized centers under 460nm light. But under 366nm light, the highest rate of NF formation was observed for samples with the biggest nanocrystal size. Under 366nm light, the smaller particles show a low rate of nitroform formation due to a more favorable band-gap electron-hole recombination. Lipid phosphatidyl-ethanolcholine (PE) under 460nm visible light in the presence of doped-TiO2 led to the formation of conjugated of double bonds in PE. This implies the formation of peroxy radicals due to the TiO2 e−cb localized electronic states under visible light irradiation.

Aspects of nitrite association with trans-[Ru(NH 3) 4P(OEt) 3H 2O] 2+

According to spectrophotometric data, the reaction of trans-[Ru(NH 3) 4P(OEt) 3(H 2O)] 2+ with NO 2 - in alkaline medium ( C H + < 10 - 9 mol L - 1 ) occurs on two steps. In the first, both the nitro ( trans-[Ru(NH 3) 4P(OEt) 3(NO 2)] +) and nitrito ( trans-[Ru(NH 3) 4P(OEt) 3(ONO)] +) isomers are formed. In the second step, the nitrito isomer is converted into the nitro form. Under equilibrium conditions and using pyrazine as auxiliary ligand, the formation constant, K N, of trans-[Ru(NH 3) 4P(OEt) 3(NO 2)] + (5.2 ± 0.6) × 10 3 M −1 (pH 11.0; μ = 0.3 mol L −1 NaCF 3COO; T = (25 ± 0.2) °C) was measured using the Indicator Colorimetric Method. The spectrophotometrically measured specific rate constant for the equation of the nitrite ligand in trans-[Ru(NH 3) 4P(OEt) 3(NO 2)] +, was (1.2 ± 0.3) × 10 −1 s −1(pH 10.9; μ = 0.3 mol L −1 NaCF 3COO; T = (25 ± 0.2) °C). Trans-[Ru(NH 3) 4P(OEt) 3NO 2] + was quantitatively converted into the trans-[Ru(NH 3) 4P(OEt) 3NO] 3+ in acid solutions ( C H + > 10 - 5 mol L - 1 ; k obs = 2.2 × 10 −3 s −1 at pH 4). However the inverse conversion was not quantitative.

Crystal Structures of the Potassium and Silver Salts of Nitroform

AbstractThe solid state structures of three nitroformate (NF) salts were determined using single crystal X‐ray crystallography. The NF anion was found to be a non‐planar moiety which adopts either the commonly observed C2v conformation or distorted propeller conformation (D3) in the case of the silver salts, or, a C2 conformation in the case of the potassium salt. This latter C2 conformation has been uniquely observed for potassium nitroformate. All structures exhibit cation‐anion interactions that influence the structure of the anion. The 13C and 14N NMR spectra of the NF anion show broad singlets, which indicates the equivalence of the nitro groups in solution within the NMR time‐scale. In addition, the vibrational and mass spectra of potassium nitroformate and silver nitroformate monohydrate were recorded. Furthermore, the gaseous decomposition products of potassium nitroformate at 25 °C were detected using IR spectroscopy and mass spectrometry.

Mapping the Triplet Potential Energy Surface of 1-Methyl-8-nitronaphthalene

Spin-unrestricted calculations and time-dependent DFT were used to characterize structure and reactivity of 1-methyl-8-nitronaphthalene (1) in the triplet state. Four hybrid models (B3LYP, PBE0, MPW1K, BHLYP) with significantly different amount of the exact exchange were employed. The triplet potential energy surface of 1 was mapped by using the UB3LYP and UMPW1K techniques. Both hybrid models provided qualitatively consistent pictures for the potential energy landscape. Thirty-one stationary points, of which 15 were minima, were found at the UB3LYP level of theory. Three minima corresponding to the nitro form of 1 were located on the triplet surface; just one was found for the singlet ground state. Two reaction paths leading from 1 either to a nitrite-type intermediate (2) or to the aci-form (3) were characterized. For both paths, reaction products were of diradical nature. The lower activation energy was obtained for the triplet-state tautomerization affording 3. The ground state of triplet multiplicity was predicted for two isomers of the aci-form. The triplet diradical 3 is expected to react through the thermal population of a close-lying singlet excited state. The results are discussed in relation to mechanisms of photoinduced rearrangements of peri-substituted nitronaphthalenes that can be used to develop novel photolabile protecting groups.

Nitrite elimination and hydrolytic ring cleavage in 2,4,6-trinitrophenol (picric acid) degradation.

Two hydrogenation reactions in the initial steps of degradation of 2,4,6-trinitrophenol produce the dihydride Meisenheimer complex of 2,4,6-trinitrophenol. The npdH gene (contained in the npd gene cluster of the 2,4,6-trinitrophenol-degrading strain Rhodococcus opacus HL PM-1) was shown here to encode a tautomerase, catalyzing a proton shift between the aci-nitro and the nitro forms of the dihydride Meisenheimer complex of 2,4,6-trinitrophenol. An enzyme (which eliminated nitrite from the aci-nitro form but not the nitro form of the dihydride complex of 2,4,6-trinitrophenol) was purified from the 2,4,6-trinitrophenol-degrading strain Nocardioides simplex FJ2-1A. The product of nitrite release was the hydride Meisenheimer complex of 2,4-dinitrophenol, which was hydrogenated to the dihydride Meisenheimer complex of 2,4-dinitrophenol by the hydride transferase I and the NADPH-dependent F(420) reductase from strain HL PM-1. At pH 7.5, the dihydride complex of 2,4-dinitrophenol is protonated to 2,4-dinitrocyclohexanone. A hydrolase was purified from strain FJ2-1A and shown to cleave 2,4-dinitrocyclohexanone hydrolytically to 4,6-dinitrohexanoate.

Molecular motions in the solid state: the thermochromic nitro-nitrito Interconversion in nickel(II) bis(diamine) complexes.

The NO(2)(-) ion, in the trans-octahedral [Ni(II)(N,N'-dimethylethylenediamine)(2)(NO(2))(2)](H(2)O) complex, coordinates the metal through the nitrogen atom (nitro form). On heating the solid complex, the anion rotates to give nitrito coordination (oxygen bound), according to a reversible process. The coordination mode of NO(2)(-) to Ni(II) is related to the steric interplay between the anion and the alkyl substituents on the diamine.

Improved synthesis of the bifunctional chelating agent 1,4,7,10-tetraaza-N-(1-carboxy-3-(4-nitrophenyl)propyl)-N′,N″,N‴-tris(acetic acid)cyclododecane (PA-DOTA)

A concise synthesis of the bifunctional chelating agent 1,4,7,10-tetraaza-N-(1-carboxy-3-(4-nitrophenyl)propyl)-N′,N″,N‴-tris(acetic acid)cyclododecane (PA-DOTA) is reported. Difficulties involving the production of partially alkylated products and their removal have been addressed and obviated. After the pure nitro form of PA-DOTA was obtained, conversion to the isothiocyanato form PA-DOTA (1 , conjugation to HuCC49 and HuCC49ΔCH2 monoclonal antibodies was achieved. Subsequent radiolabeling with 177Lu was performed, demonstrating a useful bifunctional chelating agent suitable for clinical radioimmunotherapy applications.

Spontaneous and base-catalyzed nitrito to nitro linkage isomerization of trans-[Co(NH 3) 4(NH 2CH 3)ONO] 2+ complex

The nitrito ion trans-[Co(NH 3) 4(NH 2CH 3)ONO] 2 rearranges to its nitro form trans-[Co(NH 3) 4 (NH 2CH 3)NO 2] 2 in aqueous base according to the rate law k obs=k s+k bc[OH −]. At μ=1.0 M, 25°C k s=1.01×10 −4 s −1; ΔH s ∗=98 kJ mol −1; ΔS s ∗=7 JK −1; k bc=3.3×10 −2 M −1 s −1; ΔH∗ bc=121 kJ mol −1; ΔS∗ bc=132 JK −1 mol −1. The base-catalyzed isomerization proceeds enterely via an intramolecular conjugate-base mechanism. The reaction is fully retentive and trans-[Co(NH 3) 4(NH 2CH 3)NO 2] 2 is the only species that could be detected by 1H nmr after the reaction was completed. The results are discussed in the light of the reaction mechanisms proposed so far and in relation to the normal substitution chemistry of pentaamminecobalt(III) complexes.