Oxo Substituents Research Articles

Cobalt(II) Single-Ion Magnet Coordinated by Double Deprotonation of 2,2'-Bipyridine-6,6'-diol Ligands.

In this study, we synthesized a new Co(II) complex, [NMe4]2[Co(bpyO2)2] (1), using deprotonated 2,2'-bipyridine-6,6'-diol ligands (bpyO2 2-). This compound exhibits a significant zero-field splitting (D) value. The far-infrared magneto spectroscopy and high-frequency and field electron paramagnetic resonance (HFEPR) measurements indicated that compound 1 possesses D = -54.8 cm-1 and E ∼ 0 cm-1. These findings were subsequently confirmed by other experimental data, including DC magnetic susceptibilities and variable temperature and variable magnetic field reduced magnetizations. Additionally, we conducted a series of AC magnetic susceptibility measurements to investigate the kinetics of magnetization relaxation. Below 6.6 K and under zero external magnetic field, fast quantum tunneling of magnetization (QTM) dominates (∼570 Hz), and temperature-independent out-of-phase signals are observed. Above 8.1 K, temperature-dependent behavior is observed. Furthermore, we examined the AC magnetic susceptibility behavior under external magnetic fields ranging from 300 to 4000 G. The effect of QTM is significantly reduced in the presence of an external magnetic field. Temperature-dependent behavior is primarily governed by Raman relaxation. Through structural analysis of compound 1 and a series of pure nitrogen-coordinated single-ion magnets (SIMs), we propose that the oxo substituents from the double-deprotonated form of the 2,2'-bipyridine-6,6'-diol ligands donate their negative charge to the pyridine ring, forming amido anion sites. This triggers a more pronounced out-of-phase signal than that observed in pure pyridine-coordinated compounds. Moreover, we observed intermolecular interactions, including intermolecular hydrogen bonding, which, to some extent, influenced the slow relaxation of molecules. Therefore, we speculate that the slow relaxation phenomenon of compound 1 may be attributed to the combination of oxo back-donating effects and intermolecular interactions.

Oligonucleotides Featuring a Covalently Mercurated 6-Phenylcarbazole Residue as High-Affinity Hybridization Probes for Thiopyrimidine-Containing Sequences.

Short oligonucleotides incorporating either 1-mercuri-6-phenylcarbazole, 8-mercuri-6-phenylcarbazole, or 1,8-dimercuri-6-phenylcarbazole C-nucleoside in the middle of the chain have been synthesized and studied for their potential as hybridization probes for sequences containing thiopyrimidine nucleobases. All of these oligonucleotides formed very stable duplexes with complementary sequences pairing the organometallic moiety with either 2- or 4-thiothymine. The isomeric monomercurated oligonucleotides were also able to discriminate between 2- and 4-thiothymine based on the different melting temperatures of the respective duplexes. DFT-optimized structures of the most stable mononuclear HgII -mediated base pairs featured a coordinated covalent bond between HgII and either S2 or S4 and a hydrogen bond between the carbazole nitrogen and N3. The dinuclear HgII -mediated base pairs, in turn, were geometrically very similar to the one previously reported to form between 1,8-dimercuri-6-phenylcarbazole and thymine and had one HgII ion coordinated to a thio and the other one to an oxo substituent.

Organo-Polyoxometalate-Based Hydrogen-Bond Catalysis.

Several urea-inserted organo-polyoxometalates (POMs) derived from polyoxotungstovanadate [P2 V3 W15 O61 ]9- were prepared. The insertion of the carbonyl into the polyoxometallic framework activates the urea toward Hydrogen-bond catalysis. This was shown on the Friedel-Crafts arylation of trans-β-nitrostyrene. Modelling shows that the most stable form of the organo-POMs features a cis-trans arrangement of the two N-H bonds, but that the likely catalytically active trans-trans form is accessible at room temperature. Finally, it is possible that the oxo substituents next to the vanadium atoms may help the approach of the nucleophile via H-bonding.

Crystal structure of ethyl 2-(3-amino-5-oxo-2-tosyl-2,5-di-hydro-1H-pyrazol-1-yl)acetate.

In the title compound, C14H17N3O5S, the five-membered ring is essentially planar. The substituents at the nitro-gen atoms subtend a C-N-N-S torsion angle of -95.52 (6)°. The amino group forms an intra-molecular hydrogen bond to a sulfonyl oxygen atom; two inter-molecular hydrogen bonds from the amino group, to the other S=O group and to the oxo substituent, form a layer structure parallel to the ab plane. The structure determination confirms that the title compound is N- rather than O-alkyl-ated.

On the influence of small chemical changes upon the supramolecular association in substituted 2-(phenoxy)-1,4-naphthoquinones

Abstract X-ray crystallography reveals the common feature of the title compounds is a 1,4-naphthoquinone ring system with a substituted phenoxy residue adjacent to an oxo-group to give 1 (H), 2 (3-Br), 3 (3-CF3), 4 (4-CN) and 5 (4-NO2). To a first approximation the fused ring system along with the two oxo substituents is planar with the major difference between the molecules relating to the relative orientations of the pendant phenoxy residues: dihedral angles range from 56.56(4)° (3) to 87.52(10)° (2). The presence of intermolecular C–H···O interactions is the common feature of the supramolecular association in the crystals of 1–5. In each of 1 and 5, these extend in three-dimensions but, only to supramolecular dimers in 4, chains in 2 and layers in 3. Each crystal also features C=O···π interactions, pointing to the importance of these points of contact in this series di-oxocompounds. In 2, these, along with C–Br···π interactions lead to a three-dimensional architecture. For 3, the C=O···π and π···π interactions occur within the layers which stack without directional interactions between them. In 4, C–H···O and C=O···π interactions combine to give a supramolecular layer, which also stack without directional interactions in the inter-layer region. Further analysis of the molecular packing was conducted by a Hirshfeld surface analysis (HSA). This points to the significant role of H···H, C···H/H···C and O···H/H···O contacts in the packing of 1. Notably different roles for these contacts are found in the other crystals correlating with the participation of the respective substituents in the molecular packing. The HSA suggests the association between layers in 3 (weak F···F and H···F interactions) and 4 (weak H···N interactions) is contributed by the phenoxy-substituents.

3,4-Seco-12α-hydroxy-5β-cholan-3,4,24-trioic Acid, a Novel Secondary Bile Acid: Isolation from the Bile of the Common Ringtail Possum (Pseudocheirus peregrinus) and Chemical Synthesis

The major bile acids present in gallbladder bile of the common ringtail possum (Pseudocheirus peregrinus), an Australian marsupial, were isolated by preparative HPLC and identified by NMR and by comparison with synthetic standards. The major compound present (52%) was 3α,12α-dihydroxy-7-oxo-5β-cholan-24-oic acid (7-oxodeoxycholic acid), about three fourths conjugated with taurine. Also present was 3α,7β,12α-trihydroxy-5β-cholan- 24-oic acid (20%; ursocholic acid) largely in unconjugated form. In addition, 3,4-seco-12α-hydroxy-5β-cholan-3,4,24- trioic acid was present in unconjugated form and constituted 8% of biliary bile acids. Proof of the structure of this novel 3,4-seco acid was obtained by its chemical synthesis from deoxycholic acid via an intermediary 3β,4β-dihydroxy derivative that was then oxidatively cleaved with sodium periodate. As all primary bile acids have a hydroxyl or oxo substituent at C-7, the absence of such in the seco-bile acid suggests that it is a secondary bile acid, synthesized by bacterial enzymes present in the intestine.

Understanding Heme Enzyme Catalysis Starts with Their Active Site Coordination Structure: Identifying Heme Iron Axial Ligands Using Magnetic Circular Dichroism Spectroscopy

Magnetic circular dichroism (MCD) spectroscopy provides diagnostic spectral data sensitive to the identity of the axial ligands and to the spin and oxidation states of heme iron centers in proteins. In this effort, we have found the proximal ligand His93Gly myoglobin cavity mutant to be a remarkably versatile scaffold for preparation of model heme complexes of defined ligation. In particular, the difference in accessibility of the two sides of the heme iron center offers the advantage of forming ambient-temperature mixed-ligand heme model complexes, which are very difficult to prepare with model systems in organic solvents. Moreover, in the H93G Mb system, the protective environment provided by the protein allows for the formation of relatively stable oxyferrous and ferryl [Fe(IV)=O] complexes with variable ligands trans to the normally reactive dioxygen and oxo substituents. Ferrous, ferric and ferryl His93Gly Mb derivatives with various exogenous ligands have been prepared as models for native heme iron active sites ligated by proximal Lys (amines), Asp or Glu (carboxylates), Tyr (phenols), seleno-Cys (selenols), Cys (thiols) and Met (thioethers). Building upon this foundation, we have focused our attention on the use of the H93G Mb cavity mutant system to aid our investigation of the coordination structure of novel heme binding and transport proteins and heme-containing oxidative enzymes. (Funding NIH GM 26730)

Electronic and Molecular Structures of trans-Dioxotechnetium(V) Polypyridyl Complexes in the Solid State

The structures of novel Tc(V) complexes trans-[TcO(2)(py)(4)]Cl·2H(2)O (1a), trans-[TcO(2)(pic)(4)]Cl·2H(2)O (2a), and trans-[TcO(2)(pic)(4)]BPh(4) (2b) were determined by X-ray crystallography, and their spectroscopic characteristics were investigated by emission spectroscopy and atomic scale calculations. The cations adopt a tetragonally distorted octahedral geometry, with a trans orientation of the apical oxo groups. trans-[TcO(2)(pic)(4)]BPh(4) has an inversion center located on technetium; however, for trans-[TcO(2)(py)(4)]Cl·2H(2)O and trans-[TcO(2)(pic)(4)]Cl·2H(2)O, a strong H bond formed by only one of the oxo substituents introduces an asymmetry in the structure, resulting in inequivalent trans Tc-N and Tc═O distances. Upon 415 nm excitation at room temperature, the complexes exhibited broad, structureless luminescences with emission maxima at approximately 710 nm (1a) and 750 nm (2a, 2b). Like the Re(V) analogs, the Tc(V) complexes luminesce from a (3)E(g) excited state. Upon cooling the samples from 278 to 8 K, distinct vibronic features appear in the spectra of the complexes along with increases in emission intensities. The low temperature emission spectra display the characteristic progressions of the symmetric O═Tc═O and the Tc-L stretching modes. Lowest-energy, triplet excited-state distortions calculated using a time-dependent theoretical approach are in good agreement with the experimental spectra. The discovery of luminescence from the trans-dioxotechnetium(V) complexes provides the first opportunity to directly compare fundamental luminescence properties of second- and third-row d(2) metal-oxo congeners.

His93Gly Myoglobin Cavity Mutant: A Versatile Scaffold for Modeling Heme Protein Active Sites. Applications to Novel Heme Transport and Redox Proteins

The proximal ligand His93Gly myoglobin (H93G Mb) cavity mutant is a versatile scaffold for the preparation of model heme complexes of defined ligand system (1). In particular, the difference in accessibility of the two sides of the heme iron center offers the advantage of forming ambient-temperature mixed-ligand heme model complexes, which are very difficult to prepare with model systems in organic solvents. Moreover, in the H93G Mb system, the protective environment provided by the protein allows for the formation of relatively stable oxyferrous and ferryl [Fe(IV)=O] complexes with variable ligands trans to the normally reactive dioxygen and oxo substituents. His93Gly myoglobin cavity mutant complexes with various exogenous ligands have been prepared as models for native heme iron active sites ligated by proximal Lys (amines), Asp or Glu (carboxylates), Tyr (phenols), seleno-Cys (selenols), Cys (thiols) and Met (thioethers). The ferrous, ferric and ferryl H93G Mb complexes described have been characterized with magnetic circular dichroism (MCD) and UV-visible absorption spectroscopy. MCD spectroscopy provides diagnostic spectral data sensitive to the nature of the axial ligands and to the spin state and oxidation state of the active site heme iron. Building upon this foundation, we have focused our attention on the use of the H93G Mb cavity mutant system to aid our investigation of the coordination structure of novel heme binding and transport proteins and heme-containing oxidative enzymes. 1) J. Qin, R. Perera, L.L. Lovelace, J.H. Dawson and L. Lebioda, Biochemistry, 45, 3170-3177 (2006).

QSPR study of the effect of steroidal hydroxy and oxo substituents on the critical micellar concentration of bile acids

Measurements of the fluorescence intensity of 1,6-diphenylhexatriene (DPH) as a probe molecule allowed the determination of critical micellar concentrations (CMCs) for 30 bile acid (BA) molecules belonging to three linear congeneric groups, with three (Group I) and two (Group II) oxygen atoms from OH or oxo groups bound to the steroid skeleton, and glyco conjugated cholic acid and glyco conjugated cholic acid derivatives (Group III). The CMC values are related to the structure of the steroid nucleus by constructing novel molecular descriptors with 2D and 3D characteristics of topological descriptors. Namely, with conventional topological descriptors (first-order connectivity index, third-order connectivity index, Wiener-index, Balaban-index, molecular topological index, cluster count, etc.) BA molecules from the same congeneric group have identical values, so that these descriptors cannot be used to form a new model for the given congeneric group. The linear regressions (models) obtained in this work for each congeneric group relate the CMCs to this new descriptor. Statistical parameters of these models, as well as their predictivity, indicate the significance of the obtained equations, that is that the micelle formation is influenced not only by the number of OH and oxo groups in the steroid nucleus but also by their steric environment.

Design and Synthesis of 2- and 3-Substituted-3-phenylpropyl Analogs of 1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine and 1-[2-(Diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine: Role of Amino, Fluoro, Hydroxyl, Methoxyl, Methyl, Methylene, and Oxo Substituents on Affinity for the Dopamine and Serotonin Transporters

Novel derivatives of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR 12909, 1) and 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine (GBR 12935, 2) with various substituents in positions C2 and C3 of the phenylpropyl side chain were synthesized and evaluated for their ability to bind to the dopamine transporter (DAT) and the serotonin transporter (SERT). In the C2 series, the substituent in the S-configuration, with a lone-pair of electrons, significantly enhanced the affinity for DAT, whereas the steric effect of the substituent was detrimental to DAT binding affinity. In the C3 series, neither the lone electron pair nor the steric effect of the substituent seemed to affect DAT binding affinity, while sp (2) hybridized substituents had a detrimental effect on affinity for DAT. In the series, the 2-fluoro-substituted (S)-10 had the highest DAT binding affinity and good DAT selectivity, while the 2-amino-substituted (R)-8 showed essentially the same affinity for DAT and SERT. The oxygenated 16 and 18 possessed the best selectivity for DAT.

N-[4-(4-Chlorophenyl)-3-methyl-6-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridin-5-yl]benzamide

The title compound, C26H21ClN4O2, has been synthesized by the reaction of 4-(4-chloro­benzyl­idene)-2-phenyl-1,3-oxazol-5(4H)-one with 3-methyl-1-phenyl-1H-pyrazol-5-amine in glycol under microwave irradiation. All atoms of the pyrazolo[3,4-b]pyridine system, with the exception of two adjacent C atoms carrying the benzamido and oxo substituents (positions 5 and 6), lie in one plane; the displacements of the latter C atoms from this plane are 0.284 (5) and 0.847 (5) Å respectively. Only one of the two NH groups, viz. that in the dihydro­pyridinone ring, participates in the inter­molecular hydrogen bonds which link the mol­ecules into infinite chains running along the b axis

Preparation and Conformational Study of 19β,28-Epoxy-18α-olean-5-ene Derivatives

New oleanane type triterpenoids with the 5(6) double bond were prepared using partial demethylation on carbon C-4. The starting compound was 23-hydroxybetulin (1b) and the key reaction was the methylation of 19β,28-epoxy-24-nor-18α-olean-4-en-3-one (3b). The 5(6) double bond was used in preparation of new derivatives with an epoxy or oxo substituent in ring B. The conformation of ring A of new type 3-oxo oleanane derivatives with a double bond or a substituent on ring B was elucidated from vicinal coupling constants of hydrogen atoms in positions 1 and 2.

Unexpected nonplanar quinoidal substructure in an abietane terpene from Salvia candelabrum—an ab initio computational search for the simplest substitution pattern causing the nonplanarity

A recently isolated natural diterpene (candelabroquinone) unexpectedly displayed nonplanarity in its quinoidal substructure on using a variety quantum chemical methods for unrestricted geometry optimisation (PM3, HF 3-21G, HF 6-31G* and HF 6-31G**). By gradual structural simplification, it was possible to identify the minimum substitution pattern causing the nonplanarity. Appreciable alteration from planarity was found when the original three-ring compound was simplified to a two-ring structure containing a cyclohexene ring fused to the 1,4-benzoquinoidal substructure having an oxo substituent in the cyclohexene ring next to the anellation. A decreased but definite nonplanarity was still observed when the oxo group was replaced by a methyl group. On removing the methyl substituent the quinoidal ring became planar and it remained so even when the two-ring molecule was further simplified to a fully substituted one-ring system.

Nucleophilic attack on ketene, 6‐methylene‐2,4‐cyclohexadienylideneketene, 6‐oxo‐2,4‐cyclohexadienylideneketene and 4‐oxo‐2,5‐cyclohexadienylideneketene: an ab initio study

AbstractNucleophilic attack of cyanide anion at the carbonyl carbon was studied computationally at the MP2/6–311+G** level for ketene and at the MP2/6–31+G* and MP2/6–31+G*//HF/6–31+G* levels for all four title compounds. Heats of addition were computed for formation of in‐plane adducts and perpendicular adducts where the terms ‘in‐plane’ and ‘perpendicular’ indicate the direction of nucleophilic attack relative to the ketene plane. Heats of activation were also computed for the two modes of attack. For ketene (1) the in‐plane adduct is favored by 37.6 kcal mol−1 and the in‐plane transition state by 18.8 kcal mol−1. For the 6‐methylene compound (2) the in‐plane adduct is favored by 20.1 kcal mol−1 and the in‐plane transition state by 7.3 kcal mol−1. For the 6‐oxo compound (3) the in‐plane adduct is more stable by 11.2 kcal mol−1 whereas the in‐plane transition state is preferred by 8.8 kcal mol−1. For the 4‐oxo compound (4) the in‐plane adduct is favored by 19.3 kcal mol−1 but its transition state by only 2.8 kcal mol−1. The in‐plane adduct for ketene is the enolate of acetyl cyanide while the perpendicular adduct is a pyramidalized carbanion attached to a cyanocarbonyl group. Calculated NPA charges support this conclusion. The perpendicular adduct is actually the transition state for rotation about the CC bond of the ketene moiety in the in‐plane adduct, and the 37.6 kcal mol−1 enthalpy difference is closely matched by the calculated activation enthalpy for rotation about the CC bond of acetaldehyde enolate: ΔH‡ = 33.6 kcal mol−1. The smaller differences found for in‐plane vs perpendicular adduct formation for the 6‐methylene, 6‐oxo and 4‐oxo compounds are correlated with decreases in bond length alternation within the six‐membered rings which occur upon addition of the nucleophile. Less alternation may be associated with an approach to aromaticity, hence an increase in stability. Both modes of attack lead to reduced bond length alternation, but the amount of alternation is lowered more for the perpendicular adducts than for the in‐plane adducts. Changes in the CO bond lengths are also diagnostic. For all four ketenes the ketenyl CO length in the in‐plane adducts is greater than in the perpendicular adducts reflecting more single bond (enolate) character in the former and more double bond (carbonyl) character in the latter. On the other hand the lengths of the 6‐oxo and 4‐oxo CO bonds in their in‐plane adducts are smaller than in the perpendicular adducts, consistent with increased conjugation with the oxo substituent in the latter. The greater NPA charge on the 6‐oxo and 4‐oxo oxygens of the perpendicular adducts supports this conclusion. Calculated enthalpies of activation are in the order ketene > 6‐methyleneketene > 6‐oxoketene, in qualitative agreement with experimentally determined rates of hydration. Copyright © 2004 John Wiley & Sons, Ltd.

Modeling heme protein active sites with the his93gly cavity mutant of sperm whale myoglobin: complexes with nitrogen-, oxygen- and sulfur-donor proximal ligands

Recent investigations of the His93Gly (H93G) "cavity" mutant of myoglobin as a versatile scaffold for modeling heme states are described. The difference in accessibility of the two sides of the heme in H93G myoglobin makes it possible to generate mixed ligand adducts in the ferric state that are difficult to prepare with heme models in organic solvents. In addition, the protection provided to the heme by the protein environment allows for the preparation of stable oxyferrous and oxo-iron(IV) complexes at near-ambient temperatures with variable ligands trans to the normally reactive dioxygen and oxo substituents. The extensive range of possible complexes that can be generated using the H93G system is illustrated with examples involving imidazole, phenolate, benzoate, thiolate and thiol ligands bound to the proximal side of the heme iron.

Electron transfer reactions to 1-adamantyl-, 1-norbornyl chlorides, and their oxo derivatives. A theoretical study

The neutral and anionic surfaces of bicyclo[2.2.1]hepta-1-yl chloride (1-chloronorbornane 9), 1chloroadamantane (4), 2-oxo- (10) and 3-oxo-1-chloronorbornane (11), and 5-chloroadamantan2-one (5), were explored at the B3LYP DFT and at the MP2 levels. The studies explain the relative reactivity of these compounds in electron transfer (ET) SRN1 reactions mainly in relation to the position of the oxo substituent on the rigid bridge. The reactivity related to the ET dissociation of the unsubstituted halides 9, 4 and the oxo derivatives 10, 11 can be explained through a concerted-dissociative pathway. On the other hand, an stepwise ET mechanism, with radical anions as intermediates, seems the most adequate reaction path to explain the reactivity of compound 5. Besides, this pathway can also be followed by compounds 10 and 11 under appropriate experimental conditions. The activation energy for the intramolecular-ET through which the radical anions dissociate into radicals follows the order 5 > 11 > 10 in the gas phase and by simulating acetonitrile as polar solvent.

ChemInform Abstract: Diastereoselective Ring-Closing Metathesis in the Synthesis of Dihydropyrans.

An investigation into the factors influencing the diastereochemical outcome of the ring-closing metathesis based synthesis of dihydropyrans is presented in this paper. Divinyl carbinols derived from α-hydroxy carboxylic acid esters are elaborated to trienes with two diastereotopic vinyl moieties. Depending on the steric demand of the oxo substituent of the divinyl carbinol moiety (either unprotected OH, TBDMS, or benzyl ether) different diastereomers are preferrably formed upon ring-closing metathesis. An extension to diastereoselective double ring-closing metathesis in the formation of spirocycles has also been investigated.

Diastereoselective Ring-Closing Metathesis in the Synthesis of Dihydropyrans

An investigation into the factors influencing the diastereochemical outcome of the ring-closing metathesis based synthesis of dihydropyrans is presented in this paper. Divinyl carbinols derived from alpha-hydroxy carboxylic acid esters are elaborated to trienes with two diastereotopic vinyl moieties. Depending on the steric demand of the oxo substituent of the divinyl carbinol moiety (either unprotected OH, TBDMS, or benzyl ether) different diastereomers are preferrably formed upon ring-closing metathesis. An extension to diastereoselective double ring-closing metathesis in the formation of spirocycles has also been investigated.

Stereoelectronic effect on one-electron reductive release of 5-fluorouracil from 5-fluoro-1-(2-oxocycloalkyl)uracils as a new class of radiation-activated antitumor prodrugs.

A series of 5-fluoro-1-(2'-oxocycloalkyl)uracils (3-11) that are potentially novel radiation-activated prodrugs for the radiotherapy of hypoxic tumor cells have been synthesized to evaluate a relationship between the molecular structure and the reactivity of one-electron reductive release of antitumor 5-fluorouracil (1) in anoxic aqueous solution. All the compounds 3-11 bearing the 2'-oxo group were one-electron reduced by hydrated electrons (eaq-) and thereby underwent C(1')-N(1) bond dissociation to release 5-fluorouracil 1 in 47-96% yields upon radiolysis of anoxic aqueous solution, while control compounds (12, 13) without the 2'-oxo substituent had no reactivity toward such a reductive C(1')-N(1) bond dissociation. The decomposition of 2-oxo compounds in the radiolytic one-electron reduction was more enhanced, as the one-electron reduction potential measured by cyclic voltammetry in N,N-dimethylformamide became more positive. The efficiency of 5-fluorouracil release was strongly dependent on the structural flexibility of 2-oxo compounds. X-ray crystallographic studies of representative compounds revealed that the C(1')-N(1) bond possesses normal geometry and bond length in the ground state. MO calculations by the AM1 method demonstrated that the LUMO is primarily localized at the pi* orbital of C(5)-C(6) double bond of the 5-fluorouracil moiety, and that the LUMO + 1 is delocalized between the pi* orbital of 2'-oxo substituent and the sigma* orbital of adjacent C(1')-N(1) bond. The one-electron reductive release of 5-fluorouracil 1 in anoxic aqueous solution was presumed to occur from the LUMO + 1 of radical anion intermediates possessing a partial mixing of the antibonding C(2')=O pi* and C(1')-N(1) sigma* MO's, that may be facilitated by a dynamic conformational change to achieve higher degree of (pi* + sigma*) MO mixing.