Quantum-mechanical study of the interaction of glyoxal with arginine

Ab initio SCF computations indicate that the formation of an adduct of glyoxal to the guanidinium ion occurs in two steps. The first addition should occur on an NH₂ group, rather than on NHCH₃, and the formation of an unsymmetrical adduct IV is competitive and may be even favored over that of the symmetrical adduct III suggested by Takahashi. The barrier for that reaction is higher than for a similar reaction with guanine. The formation of a Schiff base between glyoxal and the guanidinium ion is disfavored because of the large endothermicity calculated for the process, much larger than that predicted for Schiff base formation with simple neutral or protonated amines.     

A DFT study of a novel oxime anticancer trans platinum complex: Monofunctional and bifunctional binding to purine bases

The first and second substitution reactions binding of the anticancer drug trans‐[Pt((CH₃)₂C?NOH)((CH₃)₂CHNH₂)Cl₂] to purine bases were studied computationally using a combination of density functional theory and isoelectric focusing polarized continuum model approach. Our calculations demonstrate that the trans monoaqua and diaqua reactant complexes (RCs) can generate either trans‐ or cis‐monoadducts via identical or very similar trans trigonal‐bipyramidal transition‐state structures. Furthermore, these monoadducts can subsequently close by coordination to the adjacent purine bases to form 1,2‐intrastrand Pt‐DNA adducts and eventually distort DNA in the same way as cisplatin. Thus, it is likely that the transplatin analogues have the same mechanism of anticancer activity as cisplatin. For the first substitutions, the activation free energies of monoaqua complexes are always lower than that of diaqua complexes. The lowest activation energy for monoaqua substitutions is 16.2 kcal/mol for guanine and 16.5 kcal/mol for adenine, whereas the lowest activation energy for diaqua substitutions is 17.1 kcal/mol for guanine and 25.9 kcal/mol for adenine. For the second substitutions, the lowest activation energy from trans‐monoadduct to trans‐diadduct is 19.1 kcal/mol for GG adduct and 20.7 kcal/mol for GA adduct, whereas the lowest activation energy from cis‐monoadduct to cis‐diadduct is 18.9 kcal/mol for GG adduct and 18.5 kcal/mol for GA adduct. In addition, the first and second substitutions prefer guanine over adenine, which is explained by the remarkable larger complexation energy for the initial RC in combination with lower activation energy for the guanine substitution. Overall, the hydrogen‐bonds play an important role in stabilizing these species of the first and second substitutions. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Molecular orbital theory of the hydrogen bond. 24. Ground-state water–uracil complexes

Ab initio SCF calculations with the STO -3G basis set have been performed to investigate the structural, energetic, and electronic properties of mixed water–uracil dimers formed at the six hydrogen-bonding sites in the uracil molecular plane. Hydrogen-bond formation at three of the carbonyl oxygen sites leads to cyclic structures in which a water molecule bridges N₁? H and O₂, N₃? H and O₂, and N₃? H and O₄. Open structures form at O₄, N₁? H, and N₃? H. The two most stable structures, with energies of 9.9 and 9.7 kcal/mole, respectively, are the open structure at N₁? H and the cyclic one at N₁? H and O₂. These two are easily interconverted, and may be regarded as corresponding to just one “wobble” dimer. At 1 kcal/mole higher in energy is another “wobble” dimer consisting of an open structure at N₃? H and a cyclic structure at N₃? H and O₄. The third cyclic structure at N₃? H and O₂ collapses to the “wobble” dimer at N₃? H and O₄. The two “wobble” dimers are significantly more stable than the open dimer formed at O₄, which has a stabilization energy of 5.4 kcal/mole. Uracil is a stronger proton donor to water through N₁? H than N₃? H, owing to a more favorable molecular dipole moment alignment when association occurs through H₁. Hydration of uracil by additional water molecules has also been investigated. Dimer stabilization energies and hydrogen-bond energies are nearly additive in most 2:1 water:uracil structures. There are three stable “wobble” trimers, which have stabilization energies that vary from 7 to 9 kcal/mole per water molecule. Hydrogen-bond strengths are slightly enhanced in 3:1 water:uracil structures, but the cooperative effect in hydrogen bonding is still relatively small. The single stable water–uracil tetramer is a “wobble” tetramer, with two water molecules which are relatively free to move between adjacent hydrogen-bonding sites, and a stabilization energy of approximately 8 kcal/mole per water molecule. Within the rigid dimer approximation, successive hydration of uracil is limited to the addition of one, two, or three water molecules.     

Structure electronique des complexes acide-base de Lewis. I. Structure electronique et conformation moléculaire des molécules F3P·BH3 et F2HP·BH3

The electronic structure and preferred conformations of F₃P·BH₃ and F₂HP·BH₃ are investigated in the framework of the CNDO /2 approximation. In complete agreement with microwave data, the staggered conformations are predicted to be the most stable ones. The barriers to internal rotation are in good agreement with experimental values (F₃P·BH₃: calc. = 3.03 kcal/mole, exp. = 3.24 ± 0.15 kcal/mole; F₂HP·BH₃: calc. = 3.63 kcal/mole, exp. = 4.05 ± 0.45 kcal/mole) and a bicentric energy partitioning shows that the variations of the total energy are completely reflected by the only variation of the interaction energy between phosphorus and H atoms bonded to boron. The analysis of the electron densities reveals the importance of the 3s(P) → 2p_x(B) transfer in the formation of the co-ordination. Finally, the computed dipole moment value and direction agree with corresponding experimental data.     

Molecular orbital theory of the hydrogen bond. XXX. Water-cytosine complexes

Ab initio SCF and SCF -CI calculations with the STO -3G basis set have been performed to investigate the structures and energies of water–cytosine complexes and the intermolecular water–cytosine surface in the cytosine molecular plane. Although there are six nominal hydrogen-bonding sites in this plane, only three dimers are distinguishable in the ground state. The most stable has an energy of ?10.7 kcal/mol, and is found in the N₁? H and O₂ region. An asymmetric cyclic structure in which the water molecule bridges adjacent N₁? H and O₂ sites is the preferred form of this dimer. The dimer in the region between O₂ and N₄? H′ of the amino group is slightly less stable at ?10.4 kcal/mol, and also has an asymmetric cyclic structure as the preferred structure, with the water molecule bridging amino N₄? H′ and N₃ hydrogen-bonding sites. The third dimer has the amino group as the proton donor to water through the hydrogen cis to C₅, and a stabilization energy of ?7.0 kcal/mol. The water-cytosine surface is characterized by deeper minima and higher barriers than the water-thymine surface and by a decreased mobility of the water molecule between adjacent hydrogen-bonding sites. Absorption of energy by the C₂?O group leads to the first n → π* excited state in which interactions of water with O₂ are broken. The water-cytosine dimers remain bound in this state, but may change structurally. In the second n → π* state interactions between water and N₃ are no longer stabilizing. As a result, the dimer in the O₂ and N₄? H′ region collapses to either a dimer with water the proton donor to O₂, or one with N₄? H′ the proton donor to water. The other two dimers remain bound. All excited dimers are destabilized on vertical excitation relative to the ground state.     

Asymmetric Synthesis of α-Amino Phosphonic Acids using Stable Imino Phosphonate as a Universal Precursor

A practical method for synthesizing chiral α-amino phosphonic acid derivatives was developed. Readily available and stable N-o-nitrophenylsulfenyl (Nps) imino phosphonate was utilized as a substrate for a highly enantioselective Friedel–Crafts-type addition of indole or pyrrole nucleophiles catalyzed by chiral phosphoric acid. The resulting adduct was easily converted into N-9-fluorenylmethyloxycarbonyl (Fmoc) amino phosphonic acid, which is useful for synthesizing peptides containing an amino phosphonic acid.     

Heterocycles. CII. Barriers to rotation in some N′-Heteroaryl N,N-dimethylformamidines

The free energies of activation about the =CH? NMe₂ bond in N′-heteroaryl N,N-dimethylformamidines have been found in the range from 15.6 kcal/mole to 23 kcal/mole.     

Heterocycles. CLXIX. Barriers to rotation in some N,N-Dimethyl-N′-heteroaryl,N,N-Diethyl-N′-heteroaryl-substituted formamidines and N,N-Dimethyl-N′-heteroaryl-substituted acetamidines

The free energies of the rotational barriers, ΔG*, about ?CH? NMe₂ bond in N′-heteroaryl N,N-dimethylformamidines (A), about ?CH? NEt₂ bond in N-heteroaryl N,N-diethylformamidines (B), and about ?C(Me)? NMe₂ bond in N′-heteroaryl N,N-dimethylacetamidines (C) have been found to be in the range 17.5–20.1 kcal/mole for type A, 18.8–21.6 kcal/mole for type B and 13–14 kcal/mole or below for type C of compounds, respectively. The compounds of the types A and B exist in the forms IIa, IIIa, IV, V, and VI, while the compounds of the type C exist in the forms IIb and IIIb.     

A theoretical study of the relative affinities of an aliphatic and an aromatic bisguanylhydrazone for the minor groove of double-stranded (dA-dT) n oligomers

The nonintercalative binding of an aliphatic and an aromatic bisguanylhydrazone (BGH) to the minor groove of double-stranded (dA-dT) _n oligomers is investigated by means of theoretical computations. The preferred binding arrangements of both BGHs are stabilized by a number of H-bonding interactions with sites O₂(T), N₃(A) and o₁ on the two strands, and require limited conformational rearrangements of the BGHs around their C-C single bonds. The intermolecular interaction energy is larger with the aliphatic BGH than with the aromatic one. The energy difference is, however, considerably reduced when the oligomer is lengthened: it passes from 16.1 kcal/mole at the heptamer level, to 7.9 kcal/mole at the undecamer level and to 4.6 kcal/mole when each strand of the undecamer is flanked with a complementary complete helical turn of phosphates, on both the 3 and 5 termini.The interaction energies of the BGHs with water molecules in the first hydration shell are, however, also larger with the aliphatic BGH, than with the aromatic BGH. This energy difference is further enhanced when one considers also the water molecules in the second shell. It becomes greater than the difference in the interaction energy of the two BGHs with (dA-dT) _n for large values of n. When the dehydration energy of BGHs is taken into account the overall energy balance is then more favorable for the interaction of the aromatic than of the aliphatic BGH with the polynucleotide. This last conclusion is in agreement with experimental results.     

Protonenresonanz-Untersuchungen an N,N-Dialkylaminoboranen. Substituentenabhängigkeit der Rotationsbarriere um die N?B-Bindung 1,2

The substituent dependence of the rotation barriers around the N? B bond in a series of N,N-dialkylaminoboranes was investigated by NMR. It was found that (1) there is a significant dependence on the size of the substituent, which arises from a ‘steric hindrance of mesomerism’ and (2) in certain cases exceptional facilitation of rotation occurs when alkyl groups on the boron atom are replaced by a chlorine atom or a second amino group. The lowering of the rotation barrier by about 10 kcal/mole in bisamino compounds compared with the corresponding monoamino compounds is explained on the basis of a lowering of the double bond character of each N? B bond owing to the participation of two N-atoms in the mesomerism of the ground state. This effect is much larger with amino groups than with chlorine atoms.     

Stereochemistry of nitrogen heterocycles. 62. Conformational analysis of isomers of 2-methyl-cis-decahydro-5-quinolinol

Isomers of 2-methyl- and 1,2-dimethyl-cis-decahydro-5-quinolinol with a syn orientation of the hydroxy and amino groups and different orientations of the methyl group relative to the methylene group at C₍₈₎H₂ were subjected to conformational analysis. In the case of a cis orientation of the methyl and methylene groups the equilibrium is shifted completely to favor the conformation with an intramolecular hydrogen bond, whereas in the case of their trans orientation the mole fraction of this conformation amounts to 21–24% for the secondary amino alcohol and 18–21% for the tertiary amino alcohol. The energies of the hydrogen bonds were determined from the intensities of the absorption bands of the free and associated hydroxy groups in the IR spectra: for the secondary hydroxy amine, according to the band of the free hydroxy group, G⁰ _OH/N is –0.8 kcal/mole, whereas, according to the band of the associated hydroxy group, it is –0.9 kcal/mole; the values for the tertiary hydroxy amine are, respectively, –0.7 and –0.8 kcal/mole.See [1] for Communication 61.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1514–1519, November, 1987.     

AB initio SCF LCAO MO study of the HOH…Cl− hydrogen bond

Ab initio SCF LCAO MO calculations for the [H₂O…Cl]^? complex have been performed. The energy of the linear hydrogen bond has been found to be lower than the energy of the bifurcated one. The difference of the energies is about 3 kcal/mole. The calculated equilibrium distance between the oxygen and chlorine atoms equals 5.75 au. The interaction energy of the chlorine anion and the rigid water molecule amounts to ?19 kcal/mole. The optimization of the OH bond length in the complex (linear hydrogen bond) leads to an interaction energy of ?19.5 kcal/mole (the experimental value equals ?13.1 kcal/mole). As a result of the hydrogen bond formation the OH bond length increases by 0.08 au.     

Kinetics of CN reactions with N2O and CO2

The rate constants for the reaction of CN with N₂O and CO₂ have been measured by the laser dissociation/laser-induced fluorescence (two-laser pump-probe) technique at temperatures between 300 and 740 K. The rate of CN + N₂O was measurable above 500 K, with a least-squares averaged rate constant, k = 10^−11.8±0.4 exp(−3560 ± 181/T) cm³/s. The rate of CN + CO₂, however, was not measurable even at the highest temperature reached in the present work, 743 K, with [CO₂] ⩽ 1.9 × 10¹⁸ molecules/cm³. In order to rationalize the observed kinetics, quantum mechanical calculations based on the BAC-MP4 method were performed. The results of these calculations reveal that the CN + N₂O reaction takes place via a stable adduct NCNNO with a small barrier of 1.1 kcal/mol. The adduct, which is more stable than the reactants by 13 kcal/mol, decomposes into the NCN + NO products with an activation energy of 20.0 kcal/mol. This latter process is thus the rate-controlling step in the CN + N₂O reaction. The CN + CO₂ reaction, on the other hand, occurs with a large barrier of 27.4 kcal/mol, producing an unstable adduct NCOCO which fragments into NCO + CO with a small barrier of 4.5 kcal/mol. The large overall activation energy for this process explains the negligibly low reactivity of the CN radical toward CO₂ below 1000 K. Least-squares analyses of the computed rate constants for these two CN reactions, which fit well with experimental data, give rise to for the temperature range 300–3000 K.     

Kinetics of the I2-catalyzed isomerization of allyl chloride to cis- and trans-1-chloro-1-propene. The stabilization energy of the chloroallyl radical

The I₂-catalyzed isomerization of allyl chloride to cis- and trans- l-chloro-l-propene was measured in a static system in the temperature range 225–329°C. Propylene was found as a side product, mainly at the lower temperatures. The rate constant for an abstraction of a hydrogen atom from allyl chloride by an iodine atom was found to obey the equation log [k,/M^?1 sec^?1] = (10.5 ± 0.2) ?; (18.3 ± 10.4)/θ, where θ is 2.303RT in kcal/mole. Using this activation energy together with 1 ± 1 kcal/mole for the activation energy for the reaction of HI with alkyl radicals gives DH⁰ (CH₂CHCHCl? H) = 88.6 ± 1.1 kcal/mole, and 7.4 ± 1.5 kcal/mole as the stabilization energy (SE) of the chloroallyl radical. Using the results of Abell and Adolf on allyl fluoride and allyl bromide, we conclude DH⁰ (CH₂CHCHF? H) = 88.6 ± 1.1 and DH⁰ (CH₂CHCHBr? H) = 89.4 ± 1.1 kcal/ mole; the SE of the corresponding radicals are 7.4 ± 2.2 and 7.8 ± 1.5 kcal/mole. The bond dissociation energies of the C? H bonds in the allyl halides are similar to that of propene, while the SE values are about 2 kcal/mole less than in the allyl radical, resulting perhaps more from the stabilization of alkyl radicals by α-halogen atoms than from differences in the unsaturated systems.     

Theoretical study of isomerism in protonated forms of N2O,NPO, and P2O

The geometric parameters of the isomers HN₂O⁺, HPNO⁺, and HP₂O⁺ were calculated by the nonempirical SCF/3-21G* method and their relative energies were determined with consideration of the electronic correlation in the MP3/DEHD + PS approximation. According to the calculations, protonation of N₂O, PNO, and P₂O molecules should preferably take place at the oxygen atom. Isomers with a quasilinear NNO and PNO backbone are most advantageous in HN₂O⁺ and HPNO⁺, and cyclic isomers are 60 and 30 kcal/mole less stable, respectively. On the contrary, the cyclic form is more stable for HPO ₂ ⁺ (by 10 kcal/mole). The bond at the attacked atom usually weakens (breaks) and the neighboring (opposite) bonds are strengthened in protonation. Protonation of P₂O stabilizes the cyclic isomer by 15 kcal/mole more strongly than the "open" isomer, resulting in inversion of their position on the energy scale. In the case of N₂O and PNO, the relative position of the cyclic and basic isomers virtually does not change, but the linear NPO isomer is destabliized. The stability of the cyclic isomers in comparison to the "open" isomers increases on substitution of N atoms by P atoms in both molecules of N₂O, PNO, and P₂O and in their ions HN₂O⁺, HPNO⁺, and HP₂O⁺. This tendency probably holds in subsequent transition to As and Sb atoms.Institute of New Chemical Problems, Russian Academy of Sciences, 142432 Chernogolovka. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 1, pp. 126–134, January, 1992.     

Conformational analysis of 1,2,3,4-tetrahydroisoquinolines

Ring and nitrogen inversion account for the conformational equilibria of 3-phenyl-1, 2,3, 4-tetrahydroiso-quinolines. In order to quantitate the relative contribution of each conformer to the equilibrium, we undertook a molecular mechanics study on several substituted 3-phenyl-1, 2, 3, 4-tetrahydroisoquinolines. Predictions from calculations were checked against cmr chemical shift data. No boat conformation contributed significantly to the equilibrium. A general result of our calculations is that in all cases the 3-phenyl group in the equatorial position is strongly favored (by at least 2.50 kcal/mole). For 3-phenyl-1, 2, 3, 4-tetrahydroisoquinolines without substitution at nitrogen, N-H in equatorial position is preferred over the axial conformer, although the energy difference between both is always small (0.30–1.10 kcal/mole). For the cis-1,3-disubstituted compounds the le'3e conformers are the only species present (at least 99.8%). The calculated energy differences between the la′3a conformer and the le′3e conformer are always large (3.80–6.10 kcal/mole for the NHe conformers and 3.60–3.80 kcal/mole for the NHa conformers). The lack of a γ_1a upfield shift at C3 also points to the preference for the pseudoequatorial-equatorial conformer. For N-methyl-3-phenyl-1,2,3,4-tetrahydroisoquinoline a preference for the NMe group in the equatorial position is predicted (0.60–2.00 kcal/mole). The small downfield shift at C4 (γ_Na = 0.5 ppm) is consistent with the equatorial NMe preference. For the cis-1,2,3-trisubstituted compounds no significant γ_1a effect at C3 (γ_1a = -0.2 and 1.0 ppm) or γ_Na effect at C4 (γ_Na = 0.1 and 0.4 ppm) is observed. For these compounds, deformations due to steric congestion are evidenced by the deviation from the values of the C4a-C8a-Cl-N and C4a-C4-C3-N torsional angles, as compared to less crowded 3-phenyl-1,2,3,4-tetrahydroisoquinolines. Here the heterocyclic ring adopts a distorted half-chair conformation.     

Formation of an Imino‐Stabilized Cyclic Tin(II) Cation from an Amino(imino)stannylene

The novel amino(imino)stannylene 1 was prepared by conversion of HNIPr (NIPr=bis(2,6‐diisopropylphenyl)imidazolin‐2‐imino) with one equivalent of Lappert’s tin reagent (Sn[N(SiMe₃)₂]₂). Treatment of 1 with DMAP (4‐dimethylaminopyridine) yields its Lewis acid–base adduct 2 . The reaction of 1 with one equivalent of trimethylsilyl azide results in replacement of the amino group at the tin center by an N₃ substituent with concomitant elimination of N(SiMe₃)₃ to afford dimeric [N₃SnNIPr]₂ ( 3 ). Remarkably, the reaction of 1 with B(C₆F₅)₃ produces the novel tin(II) monocation 4 ⁺[MeB(C₆F₅)₃]^? comprising a four‐membered stannacycle through methyl‐abstraction from the trimethylsilyl group.     

Duplex‐Stabilization Properties of Oligodeoxynucleotides Containing N2‐Substituted Guanine Derivatives

Oligodeoxynucleotides 3 – 13 carrying different guanine derivatives with substituents at the N² position have been prepared from a common precursor. Duplexes containing these modified bases are more stable than unmodified duplexes. The highest stability is found in guanine derivatives carrying at N² an ethyl and propyl group substituted with a group that is protonated under physiological conditions, which is compatible with a possible interaction of the protonatable group with the phosphates.     

IR absorption spectra of 1-aryl-3-pyrazolidones

An examination of the frequencies and intensities of the valence vibration bands of carbonyl groups established that the phenyl group interacts with the C=O group of 1-phenyl-3-pyrazolidone and its m- and p-tolyl derivatives in solution. It is assumed that the interaction is accomplished through the N₁ and N₂ atoms in the sp² state. 1-Phenylpyrazolidone derivatives are strongly associated in CC1₄ and CHCl₃ solutions. The association decreases on passing from CCl₄ to CHCl₃ solutions and when there are methyl groups in the ortho positions of the phenyl rings. The energy of association between the 1-phenylpyrazolidones and organic bases (acetonitrile, ethyl acetate, and dioxane), evaluated from the shift in _nh, is 1.36–3.5 kcal/mole. The frequencies and integral intensities of the bands of the C=O and NH groups in chloroform were measured.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1678–1682, December, 1970.     

Pulsed NMR study of molecular motion in the uncured diglycidyl ether of bisphenol-A

The diglycidyl ether of bisphenol-A, an uncured epoxy resin, has been studied by pulsed NMR. Values of the proton relaxation times T₁, T_1p, and T₂ have been measured over the temperature range from ?160 to 200°C. The resin was studied in its monomeric form and in two mixtures containing higher oligomers. The relaxation times are interpreted in terms of the molecular motion in the resins. The motion responsible for relaxation in the solid monomer form is thought to be methyl group reorientation at low temperatures and general molecular motion at high temperatures. The motions are characterized by activation energies of 5 kcal/mole and 33 kcal/mole, respectively. The solid mixtures exhibit similar effects to the monomer, but an additional relaxation mechanism is observed which is attributed to segmental motion. This motion is characterized by an activation energy of 12–15 kcal/mole. The self-diffusion coefficient was measured in the liquid monomer, and the activation energy for self-diffusion is found to be 11 kcal/mole.