Quantum-chemical study of the photoisomerization and photocyclization reactions of styrylquinolines: Potential energy surfaces

The cross sections of potential energy surfaces (PES) for the S₀ and S₁ states were calculated by the semiempirical PM3 and PM3-CI (8 × 8) methods, respectively, along the reaction coordinate of the isomerization and cyclization of 2- and 4-styrylquinolines (SQ). The PES of the S₀ state exhibits three minima separated by the transition-state barriers of isomerization and cyclization corresponding to three isomeric SQ forms, the E- and Z-isomers and the dihydrogenated cyclic product. On the PES of the S₁ state, the “perpendicular minimum” at dihedral angle values of ～ 90° corresponds to the transition state of the isomerization reaction and the pericyclic minimum with a distance of 1.7–2.0 Å between the atoms involved in cyclization corresponds to the transition state of the cyclization reaction. With simultaneous scanning of the PES of the S₁ state along the isomerization and cyclization reaction coordinates, the minimal-energy path was found for 4SQ, which makes it possible to explain the formation of the photocyclization product in the single-photon process upon irradiation of the E-isomer. It was found that the PM3 method overestimates the stability of the structures in which the aromatic ring is oriented perpendicular to the plane of the molecule, resulting in virtual minima on the PES of the S₁ states.     

Comparative semiempirical and DFT study of styrylnaphthalenes and styrylquinolines and their photocyclization products

Semiempirical molecular orbital (PM3, PM6, and RM1) and density functional theory (DFT) (B3LYP/6‐31G*) studies are carried out for 1‐ and 2‐styrylnaphthalenes and their aza‐derivatives—2‐ and 4‐styrylquinolines. Relative stabilities of three isomeric forms: E‐ and Z‐isomers and the closed‐ring dihydrocyclophotoproduct (derivative of dihydrophenanthrene) are calculated. Compared to PM3, PM6 and especially RM1 understate heats of formation; in some cases, PM6 and RM1 even place Z‐isomer in energy below E‐isomer. PM3 rather close to DFT predicts heats of isomerization reaction, whereas PM6 and especially RM1 underestimate these values. Semiempirical methods in comparison with DFT markedly underestimate heats of cyclization reaction; however, reproduce trends in relative stabilities of different isomers in dependence on the structure of styrylnaphthalenes and styrylquinolines. Qualitative correlation is found between calculated relative stabilities of the closed‐ring forms (heats of cyclization reaction) and experimental data: cyclized products with low heats of cyclization are observed in steady‐state photolysis and those with high heats of cyclization are not. In the latter case, the closed‐ring compounds, if formed in the excited state, due to thermal instability decompose rapidly with ring opening in the ground state that prevents their observation. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Pericyclic and Heteroelectrocyclic Mechanisms for the Cyclization of 1,3,5-Hexatrien-1-one and Its 6-Aza Analog

The cyclization of 1,3,5-hexatrien-1-one, 1, and the Z- and E-isomers of 1-aza-1,3-butadienylketene 3 were studied using the semiempirical AM1 and PM3 methods. Cyclizations of compounds 1 and Z-3 are shown to occur via a mono-rotation mechanism with barriers of 15.49 and 32.85 kcal/mol respectively. The reactions proceed via non-planar transition states which result from rotation of the methylene group for compound 1 and the imino group for compound Z-3. Cyclization of E-3 proceeds via a non-rotatory mechanism through a planar transition state. The activation barrier is 4.83 kcal/mol (AM1). The electronic structures of the initial and final states, and of some intermediate structures, including the transition states for the cyclization of compounds 1 and 3, were analyzed by the natural orbital method using HF/6-31G*//AM1 calculations. Energetic, structural, and orbital criteria indicate the heteroelectric mechanism for the cyclization of compound E-3 and the pericyclic mechanism for the cyclization of compounds 1 and Z-3.     

An efficient synthesis of epoxydiynes and a key fragment of neocarzinostatin chromophore

[reaction: see text] A key structural feature of the Neocarzinostatin chromophore is a reactive epoxydiyne. We present here a new method for the preparation of epoxydiynes by the addition of an allenyl zinc bromide to a propargylic ketone.     

An investigation of energy migration in luminescent diluted Gd3+ systems

The luminescence of yttrium-diluted Gd³⁺ compounds containing efficient trap centers is reported and discussed. By using a rough approach it is possible to derive the critical distance for energy transfer between Gd³⁺ ions. This approach implies a critical Gd³⁺ concentration above which the Gd³⁺ emission is quenched. This concentration can be related to the number of Gd³⁺ neighbors involved in the energy migration process among the Gd³⁺ ions. It is shown that the critical distance for energy transfer between Gd³⁺ depends on the ionic character of the compound. In fluorides this distance is approximately 5 Å, in oxides approximately 6.5 Å. For Gd³⁺ ions in oxides on a (nearly) centrosymmetric site, this distance is approximately 5 Å, as in the fluorides. These latter phenomena can be explained concerning the type of interaction between the Gd³⁺ ions.     

Synthetic ligands for apo-neocarzinostatin

Neocarzinostatin (NCS) is a 1:1 complex of an enediyne chromophore (NCSChrom), non-covalently bound to an 11 kDa protein (apoNCS). We are exploring apoNCS as a generic protein system for sequestering small molecules for therapeutic applications. Here, we disclose a new flavone ligand 1 for apoNCS and present a high-resolution NMR structure of this ligand bound to apoNCS. This is the first high-resolution structure of a completely non-cognate ligand bound to the apoNCS protein. This work provides unambiguous evidence that a completely new class of ligand can bind specifically to apoNCS. Furthermore, the mode of binding is different than that of the naphthoate-based ligands, and for such a simple hydrophobic compound, the new ligand surprisingly binds specifically. This work indicates that apo-Neocarzinostatin has multiple selective and distinct binding modes for small-molecule cargo.     

Reactions ofOrtho-quinones and the model compound 4-t-butyl-1,2-benzo-quinone in alkaline peroxide

The literature on the occurence and reactions of quinone structures in mechanical pulps has been reviewed. A study on the reactions of a quinone model compound (4-t-butyl-1,2-benzoquinone) in alkaline hydrogen peroxide has been reported, with detailed analysis of reaction products and kinetic phenomena. The study reveals that the diversity of products formed is much more complex than that obtained using an α,β-unsaturated aldehyde as a model, a simple second-order expression can be used to describe the kinetics. The kinetics representing chromophore removal for the two classes of model compound are compared with previously reported studies of kinetic phenomena during bleaching of mechanical pulps.     

Synthesis and fluorescence behavior of 3‐methacryamide‐9‐carbazole and its polymer 1

A novel acrylic monomer‐bearing carbazole chromophore, 3‐methacrylamide‐9‐ethyl‐carbazole and its model compound 3‐isobutyramide‐9‐ethylcarbazole were synthesized by reaction of 3‐amino‐9‐ethyl carbazole and the corresponding acyl chloride in the presence of triethylamine. It can be polymerized easily by using azo‐bisisobutyronitrile as an initiator or photopolymerized without any sensitizer. The photochemical behavior of 3‐methacrylamide‐9‐ethyl‐carbazole, its polymer and 3‐isobutyramide‐9‐ethylcarbazole were investigated by recording the fluorescence spectra in N,N‐dimethylformamide. It was found that the fluorescence intensity of the monomer is dramatically lower than those of its polymer and the model compound in the same chromophore concentration. This phenomenon, termed as the ‘structural self‐quenching effect’, was commonly observed for acrylic monomers bearing chromophore moieties and ascribed to the coexistence of the electron‐donating chromophore and the electron‐accepting double bond within one molecule. The strong fluorescence of the polymer can be quenched by adding electron‐deficient monomers having no chromophore moieties such as methyl methacrylate and acrylonitrile, and the Stern–Volmer constants were determined. It is observed that the higher the electron deficiencies of the quenchers, the higher the Stern–Volmer constants, implying a stronger quenching effect.Copyright © 2000 John Wiley & Sons, Ltd.     

Thiols screened by the neocarzinostatin protein for preserving or detoxifying its bound enediyne antibiotic

Neocarzinostatin is an antibiotic chromoprotein produced by Streptomyces carzinostaticus. Its enediyne-containing chromophore exhibits high DNA cleavage activity and belongs to one of the most potent categories of antitumor agents. The labile chromophore is readily inactivated by environmental thiols including the most abundant glutathione. How the microorganism preserves the secreted antibiotic and at the same time is immune to its toxicity are of interest. Site-directed mutagenesis studies of the neocarzinostatin protein have shown that residues D33 and D99 play primary and secondary roles, respectively, in preserving neocarzinostatin from acidic glutathione whereas D79 and other residues around the opening of the binding cleft have an insignificant effect. Biothiol analyses revealed that cells of S. carzinostaticus produced no glutathione, but instead neutral mycothiol, which is known to serve functions analogous to glutathione. Mycothiol was the only neutral-charged thiol produced by the organism; all other identified biothiols carried at least partial negative charges. When the bacteria were cultured under conditions that stimulated the biosynthesis of neocarzinostatin, the yield of mycothiol increased significantly, which suggests mycothiol-dependent cellular detoxification. Treating neocarzinostatin samples with the cell extract that retained active sulfhydryls led to efficient drug inactivation, which indicates that mycothiol is allowed to approach the protein-bound chromophore. The anionic side-chains of D33 and D99 in the neocarzinostatin protein played two critical roles in a single thiol-screening operation: Preserving the antibiotic for defense and survival by rejecting the ubiquitous glutathione through charge-charge repulsion in the outer-cell environment and detoxifying the toxin in the inner-cell body for self-resistance by accepting the cell-produced neutral mycothiol.     

The gem-disubstituent effect—a computational study that exposes the relevance of existing theoretical models

The DFT B3LYP/6-31G (d, p) and HF/6-31G calculation results for the cyclization reactions of six different di-substituted 4-bromobutylamines (Brown’s system) reveal that the driving force for accelerations in the rate for intramolecular cyclization compared to the linear unsubstituted compound is due to strain effects (difference in strain energy in the ground state and in the transition state) and not to proximity in the ground state stemming from the distribution of rotational conformations ‘near attack conformation’ (time of residence at a reactive distance). Further, the results indicate that the reaction rate (log k_rel) for the intramolecular cyclization process is strongly correlated with the distance between the two reacting centers (r) and the attack angle (α). The latter result is the first to correlate strain and reaction rate with geometrical parameters (r and α).     

Theoretical study of the N20 molecule

In the study of the N₂₀ molecule with an I_h symmetry group, the following methods were applied: 6-31G, 3-21G and STO-3G ab initio and PM3 semiempirical MO methods. Both geometrical optimization and frequency calculations are reported. Results of optimized bond distances (d_N---N), first ionization potential, ΔH_a, ΔG_a and bond energy, for the cases of 6-31G, 3-21G, and PM3 showed that the N₂₀ molecule is a highly stable compound with a delocalized N---N single bonded cluster structure.     

Preparation of Polyimides Via the Palladium-Catalyzed Carbonylation and Condensation of Tetraiodoaromatics and Diamines

Several polyimides were prepared by the palladium-catalyzed carbonylation and condensation of tetraiodoaromatic compounds and diamines. This new reaction for preparing polyimides was verified in model compound work to be an efficient, high yield route to cyclic imides. Since fully imidized groups are formed during the polymerization, it was necessary to limit the diamines to those that would impart solubility to the polymer. In contrast to the model compound work, the polymerization reaction yielded an appreciable concentration of amide functional groups due to incomplete cyclization and/or branching reactions. Thermal characterization of the polyimides formed by this process is reported.     

DIESEL-MP2: a new program to perform large-scale multireference-MP2 computations

This article presents a new MR‐MP2 code (Multi‐Reference Møller–Plesset 2nd order) suitable for the computation MR‐MP2 energies of extended systems with strong near degeneracy effects (e.g., open shell systems). It is based on the DIESEL program package developed by Hanrath and Engels. Due to improved algorithms the new code is able to handle systems with 400–500 basis functions and more than 100 electrons. The code is made for parallel computers with distributed memory, but can also be run on local machines. It possesses two integral interfaces (MOLCAS, TURBOMOLE). The algorithms are briefly introduced and timings for the Neocarzinostatin chromophore are presented. The efficiencies of the codes obtained with Intel or GNU compilers are compared. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1055–1062, 2006     

Water Diffusion In And Out Of The β-Barrel Of GFP and The Fast Maturing Fluorescent Protein, TurboGFP

The chromophore of fluorescent proteins is formed by an internal cyclization of the tripeptide 65SYG67 fragment and a subsequent oxidation. The oxidation is slow - the kinetics of this step is presumably improved in fast maturing GFPs. Water molecules can aid in the chromophore formation. We have used 50 ns molecular dynamics simulations of the mature and immature forms of avGFP and TurboGFP to examine the diffusion of water molecules in-and-out of the protein β-barrel. Most crystal structures of GFPs have well-structured waters within hydrogen-bonding distance of Glu222 and Arg96. It has been proposed that they have an important role in chromophore formation. Stable waters are found in similar positions in all simulations conducted. The simulations confirm the existence of a pore that leads to the chromophore in the rapidly maturing TurboGFP; decreased water diffusion upon chromophore formation; and increased water diffusion due to the pore formation.     

Synthesis of the fully functionalized nine-membered diyne core of the C-1027 chromophore

We report the synthesis of the fully functionalized seco-acid of the C-1027 chromophore. The key reaction is a LiN(TMS)₂/CeCl₃-promoted acetylide-aldehyde condensation to construct the highly strained nine-membered diyne. Appropriate functionalization of the substrates significantly affects the yield of the cyclization. The present findings will be the basis of further studies toward the total synthesis of the C-1027 chromophore.     

The role of the protein matrix in green fluorescent protein fluorescence

In the ground state of the highly conjugated green fluorescent protein (GFP), the chromophore should be planar. However, numerous crystal structures of GFP and GFP-like proteins have been reported with slightly twisted chromophores. We have previously shown that the protein cavity surrounding the chromophore in wild-type GFP is not complementary with a planar chromophore. This study shows that the crystal structure of wild-type GFP is not an anomaly: most of the GFP and GFP-like proteins in the protein databank have a protein matrix that is not complementary with a planar chromophore. When the pi-conjugation across the ethylenic bridge of the chromophore is removed the protein matrix will significantly twist the freely rotating chromophore from the relatively planar structures found in the crystal structures. The possible consequences of this nonplanar deformation on the photophysics of GFP are discussed. A volume analysis of the cis-trans-isomerization of HBDI, a GFP chromophore model compound, reveals that its hula-twist motion is volume conserving. This means that, if the GFP chromophore or GFP chromophore model compounds undergo a cis-trans-isomerization in a volume-constricting medium, such as a protein matrix or viscous liquid, it will probably isomerize by means of a HT-type motion.     

Polymer-aided stereodivergent synthesis (PASS): a new concept for the discrete preparation of optical antipodes

[structure: see text]. A new concept for the discrete preparation of optical antipodes is reported. The approach makes use of a cyclization/cleavage procedure that has been applied to polymer-supported quasi-meso compound 1, containing a polymeric leaving group and a regular leaving group. Two-directional cyclization leads to the formation and separation of quasi-enantiomers 2 and 3 simultaneously, with one being immobilized and one free in solution. Treatment of 2 and 3 with appropriate nucleophiles gives discrete enantiomers 4 and 5.     

Stereocontrol at the steady state in radical cyclizations of acyclic dihalides

The first examples of manipulating stereocontrol solely by reaction topography in radical cyclizations starting from acyclic precursors are reported. The kinetic model for acyclic compound stereoselection is verified experimentally by conducting a series of radical cyclizations of 1,3-dihalo-2-(1-phenyl-3-butynyl)propanes with triphenyltin hydride and measuring the ratios of the products. Monohalide intermediates are observed for the first time, and evidence that bromide- and iodide-substituted radicals have different cyclization rate constants is provided.     

Design and development of a new pyrromethene dye with improved photostability and lasing efficiency: theoretical rationalization of photophysical and photochemical properties

In an attempt to develop a photostable and efficient pyrromethene compound for use in liquid dye lasers, three congeners of the commercially available pyrromethene 567 (PM567) laser dye were synthesized and their photophysical properties, lasing efficiencies, and photochemical stabilities were studied. In general the presence of an aryl group at C-8 of the pyrromethene chromophore increased the photostability. One of the congeners possessing a C-8 trimethoxyphenyl moiety showed significantly improved lasing parameters than PM567. Compared to PM567, the photochemical stability of the new dye was 2-fold, while it showed an equivalent lasing efficiency to that of PM567 at a significantly lower concentration. The increased photostability of these new dye molecules could be explained by theoretical calculation on their capacity to generate singlet oxygen ((1)O(2)) and probability of reaction with (1)O(2). Our calculations were in agreement with the experimental results and indicated that a systematic design of new derivatives of pyrromethene chromophore might lead to improved laser dye molecules.