Molecular scissors

Easy availability of ultrafast high intensity lasers has fuelled the dream of their use as molecular scissors to cleave selected bonds (1-3). Theoretical approaches to laser assisted control of chemical reactions have kept pace and demonstrated remarkable success (4,5) with experimental results (6-9) buttressing the theoretical claims. The different tablished theoretical approaches to control have been reviewed recently (10). While the focus of these theoretical approaches has been on field design, the photodissociation yield has also been found to be extremely sensitive to the initial vibrational state from which photolysis is induced and results for (11), HI (12,13), HCl (14) and HOD (2,3,15,16) reveal a crucial role for the initial state of the system in product selectivity and enhancement. This critical dependence on initial vibrational state indicates that a suitably optimized linear superposition of the field free vibrational states may be another route to selective control of photodissociation. 

A completely different access to molecules with a scissor-like shape is opened up via spiro-linkage. Typical examples following this building principle are the spiro-bifluorenes 22 3) and 23 43 which differ also in the functional groups. In case of the spirocompounds, the flexible hinge is not applicable-and the edges of the molecular scissors are fixed at an angle of 90°. 

For example, with the crystal structure of the aspartyl protease from human immundeficiency virus (HIV-1) in 1989 came the opportunity to design molecules to block this important enzyme that acts as a molecular scissors. HIV is the virus responsible for AIDS. Essential to viral replication, the HIV protease cuts long strands composed of many proteins into the functional proteins found in mature virus particles. This proteolysis occurs at the very end of the HIV replication cycle (Figure 7-1). The three-dimensional structural information derived from the x-ray crystal structure, combined with computer modeling techniques, allowed chemists to design potent, selective inhibitors of the protease enzyme (Figure... 

Cutting DNA at precise locations. Sequence-specific endonucleases (restriction endonucleases) provide the necessary molecular scissors. 

In essence we needed a molecular editing system a pair of molecular scissors that could cut the DNA text into manageable sections a kind of molecular glue pot that would allow us to manipulate those pieces and finally a molecular duplicating machine to amplify the pieces that we had cut out and isolated (pp. 87-88). 

To accomplish site-selective DNA scission using the non-covalent strategy, we need both (i) molecular scissors that show sufficiently high substrate-specificity and (ii) hot spots" that are formed at predetermined positions in substrate DNA and are hydrolyzed preferentially by these molecular scissors. 

Molecular Scissors showing High Substrate-specificity... 

Restriction enzyme An endonuclease that cleaves DNA at a specific site restriction enzymes are the molecular "scissors" of recombinant DNA technology. 

Moffat, A. Triplex DNA Finally Comes of Age. Science 252, 1374—1375 (1991). [Triple helices as molecular scissors. ]... 

Durai, S, Mani, M., Kandavelou, K., Wu, J. et al (2005) Zinc finger nucleases custom-designed molecular scissors for genome engineering of plant and maimnalian cells. Nucleic Acids Res., 33, 5978-5990. 

The reaction between the benzohydroxamate anion (109) and bis(2,4-dinitrophenyl)phosphate (110) has been examined kinetically, and the products were characterized by mass and NMR spectroscopies. The phosphate (110) underwent nucleophilic attack of (109) on phosphorus, giving 2,4-dinitrophenolate and an unstable intermediate (111) that underwent the Lossen rearrangement to alford phenylisocyanate, aniline, diphenylurea, and O-phenylcarbamyl benzohydroxamate and (ii) attack on the aromatic carbon, giving an intermediate (112) that was detected but slowly decomposed to aniline and 2,4-dinitrophenol (Scheme 25)." The benzohydroxamate anion represented a unique type of reactive nucleophile since it behaved as a one-cut self destructive molecular scissor, which lost its... 

In the second-generation artificial ribonucleases, molecular scissors are incorporated into the inside of DNA strand in order to achieve efficient catalytic turnover. Upon scission, the RNA fragment used for the binding to DNA is divided into two small fiagments. The stability of the RNA/DNA hetero-duplex decreases as the RNA becomes shorter, so that the small RNA fragments are spontaneously removed fixnn the artificial enzymes. 

The molecular scissors can be further developed as molecular pliers (Figure 94), which can twist guest molecules by incorporating a zinc porphyrin unit at each cyclopentaduenyl ring of the ferrocene module. Owing... 

Figure 93 Molecular structures of the molecular scissor and cartoon representation of its open and close motion induced by photoisomerization of the azobenzene unit. (Reproduced from Ref. 154. American Chemical Society, 2003.)...

Figure 13 Photochemically activated molecular scissors and tweezers, (a) Structural formula and operation of molecular scissors 16. (b) Structural formula of the binary complex composed of tweezer 17 and rotary guest 18. (c) Structural formula of the ternary complex formed by tweezer 19, bridging rotor 20, and scissoring component 21. ...

The experimental realization of the optimal initial states is, however, a completely uncharted area. In an earlier paper,we have presented the formulae to obtain field parameters required to achieve these FOISTs, and the optimal control approach may also feasibly and profitably be employed to attain this FOIST, which comprises only three vibrational levels. We however believe that, while the theoretical tools are useful, the central results from our investigation - - are that, instead of putting the entire onus of selective control on a theoretically designed laser pulse that may not be easy to realize in practice, the approach where different vibrational population mixes are experimentally obtained and subjected to readily attainable photolysis pulses, leading to an empirical experimental correlation between selectivity attained for diverse photolysis pulses and initial vibrational population mix used, represents a more promising and desirable alternative. Our results, we hope, will spur experimental tests, and a concerted partnership between field and initial state shaping is required to better realize the chemical dream - of using lasers as molecular scissors and tweezers to control chemical reactions. 

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