Matthias Prall

Substituent effects on the Bergman cyclization of (Z)-1,5-hexadiyne-3-enes: a systematic computational study

The effects of several substituents (BH2, BF2, AlH2, CH3, C6H5, CN, COCH3, CF3, SiH3, NH2, NH3+, NO2, PH2, OH, OH2+, SH, F, Cl, Br) on the Bergman cyclization of (Z)‐1,5‐hexadiyne‐3‐ene (enediyne, 3) were investigated at the Becke–Lee–Yang–Parr (BLYP) density functional (DFT) level employing a 6‐31G* basis set. Some of the substituents (NH3+, NO2, OH, OH2+, F, Cl, Br) are able to lower the barrier (up to a minimum of 16.9 kcal mol−1 for difluoro‐enediyne 7rr) and the reaction enthalpy (the cyclization is predicted to be exergonic for OH2+ and F) compared to the parent system giving rise to substituted 1,4‐dehydrobenzenes at physiological temperatures.

The cyclization of parent and cyclic hexa-1,3-dien-5-ynes--a combined theoretical and experimental study.

The thermal cycloisomerization of both parent and benzannelated hexa-1,3-dien-5-yne, as well as of carbocyclic 1,3-dien-5-ynes (ring size 7-14), was investigated by using pure density functional theory (DFT) of Becke, Lee, Yang, and Parr (BLYP) in connection with the 6-31G* basis set and the Brueckner doubles coupled-cluster approach [BCCD(T)] with the cc-pVDZ basis set for the parent system. The initial cyclization product is the allenic cyclohexa-1,2,4-triene (isobenzene), while the respective biradical is the transition structure for the enantiomerization of the two allenes. Two consecutive [1,2]-H shifts further transform isobenzene to benzene. For the benzannelated system, the energetics are quite similar and the reaction path is the same with one exception: the intermediate biradical is not a transition state but a minimum which is energetically below isonaphthalene. The cyclization of the carbocyclic 1,3-dien-5-ynes, which follows the same reaction path as the parent system, clearly depends on the ring size. Like the cyclic enediynes, the dienynes were found to cyclize to products with reduced ring strain. This is not possible for the 7- and 8-membered dienynes, as their cyclization products are also highly strained. For 9- to 11-membered carbocycles, all intermediates, transition states, and products lie energetically below the parent system; this indicates a reduced cyclization temperature. All other rings (12- to 14-membered) have higher barriers. Exploratory kinetic experiments on the recently prepared 10- to 14-membered 1,3-dien-5-ynes rings show this tendency, and 10- and 11-membered rings indeed cyclize at lower temperatures.

Is SH4, the simplest 10-S-4 sulfurane, observable?

The kinetic stability of SH4 was investigated theoretically with the coupled cluster ansatz. The two possible modes of decomposition into SH2 and H2 through either a C2v or a C1 transition structure (TS) were investigated using intrinsic reaction coordinate (IRC) computations; orbital interactions along the reaction paths were analyzed. The two dissociation modes are due to differences in the electron delocalization in the TSs. While the C2v TS is bonded rather covalently by a three center–four electron (3c–4e) interaction which is lost in a strictly synchronous way (two electrons occupy the same orbital at a time along the reaction coordinate), the bonding orbital in the C1 TS is merely occupied by a single electron. Surprisingly, this highly polarized TS has a lower barrier. Computations at the CCSD(T)/cc-pVQZ level of theory show that the zero-point corrected enthalpy (ΔH0‡) of the C1 TS is 16 kcal mol−1 above the C4v symmetric ground state; the barrier along the C2v path is 40 kcal mol−1. The overall exothermicity for the dissociation into SH2 and H2 was estimated to be ΔH0=−76 kcal mol−1. The fundamental IR absorptions of SH4 (obtained by scaling the computed harmonic vibrational frequencies taken from the CCSD(T)/cc-pVQZ level of theory) are 1432 and 2037 cm−1.

VMD: a graphical tool for the modern chemists

V isual Molecular Dynamics (VMD) is a molecular graphics program distributed by the University of Illinois at Urbana–Champaign, and designed for the interactive visualization and analysis of biological systems such as proteins, nucleic acids, lipid bilayer assemblies, and membranes. It is available for SGI workstations with IRIX 5.3 or higher, Hewlett-Packard workstations with HPUX 10.20, Sun workstations with Solaris 2.6 or higher, IBM RS/6000 workstations with AIX 4.2 or higher, PCs running Windows 95/98/NT, or Linux. At its heart, this program is a general application for displaying molecules containing any number of atoms. It can read PDB files or use Babel (if available) to convert other formats automatically. Once loaded, user-defined subsets of the molecule can be displayed in various ways including simple points and lines, CPK spheres and cylinders, licorice bonds, backbone tubes, ribbons, van der Waal spheres, and molecular surfaces. The display can be saved directly to a postscript file or in a format suitable for use by ray-tracing programs such as Raster3D, POV, and Rayshade. VMD can read molecular trajectories from DCD and Amber files, or it can acquire time steps from a running molecular dynamics program. The data can be used to animate the molecule or to plot the change in molecular properties such as interatomic distances, angles, or dihedrals over time. VMD can be used as a graphical front end to a molecular dynamics (MD) program running on a remote supercomputer or high-performance workstation. VMD can interactively display and control the MD simulation as the simulation is running. The user can disconnect from the simulation and let it continue, reattach to a running simulation, or halt the MD program. A number of different visual display and control systems are supported in addition to the usual monitor, keyboard, and mouse. The UNC tracker library is used to get position and orientation information from a wide variety of spatial input devices, including a Polhemus Fastrak. An interface to the CAVE library has been developed for use in many different types of stereoprojection facilities. VMD uses the freely available Tcl scripting language for processing text commands. Further information about VMD is available from www.ks.uiuc.edu/Research/vmd/.

High Level Quantum-Chemical Computations on the Cyclizations of Enyne Allenes

The ring-closure reactions of the enediyne and enyne-allene moieties of the natural antitumor antibiotics neocarzinostatin (1), calicheamicin (4), and dynemicin (5) are held responsible for the DNA-cleavage abilities of these potent pharmacophors. Neocarzinostatin, first isolated from Streptomyces carzinostaticus in 1961 [1], consists of the key chromophore 1 (Fig. 1.1) bound to a 113-amino acid apoprotein. [2,3] The enediyne moiety of 1 is activated by a thiol nucleophile, rearranges to enyne-cumulene 2, and cyclizes to the highly reactive biradical 3 (Fig. 1.1), a reaction akin to the Myers-Saito cyclization. [4] Since 1 binds to the minor groove of DNA, [5–;7] 3 is able to abstract hydrogens from adenine or thymine moieties [8] leading to cell damage. While calicheamicin 4 and dynemicin 5 (Fig. 1.1) undergo Bergman cyclizations to give rise to 1,4-didehydrobenzene biradicals, the neocarzinostatin chromophore 1 reacts differently.