In spite of its importance in cell function, targeting DNA is under-represented in the design of small molecules. A barrier to progress in this area is the lack of a variety of modules that recognize G•C base pairs (bp) in DNA sequences. To overcome this barrier an entirely new design concept for modules that can bind to mixed GC and AT sequences of DNA is reported. Because of their successes in biological applications, minor-groove-binding heterocyclic cations were selected as the platform for design. Binding to AT sequences requires H-bond donors while recognition of the G-NH2 requires an acceptor. The concept that we report here uses preorganized N-methylbenzimidazole (N-MeBI) thiophene modules for selective binding with mixed bp DNA sequences. The interaction between the thiophene sigma-hole (positive electrostatic potential) and electron donor nitrogen of N-MeBI preorganizes the conformation for accepting an H-bond from G-NH2. The compound-DNA interactions were evaluated with a powerful array of biophysical methods and the results show that N-MeBI-thiophene monomer compounds can strongly and selectively recognize single G•C bp sequences. Replacing the thiophene with other moieties significantly reduces binding affinity and specificity, as predicted by the design concept. These results show that the use of molecular features, such as sigma-hole, can lead to new approaches for small molecules in biomolecular interactions.
The Free Hanging Solid Ballast Semisubmersible (FHSB) Semi is an innovative high performance submersible design that is suitable for the dry tree application because of its extremely low heave motion response. In this paper, the FHSB Semi has been designed to support dry tree application in the Gulf of Mexico (GoM) for similar conditions; payload, environment, water depth and number of risers such as that applied to an existing Spar platform in the GoM. Holstein Spar has been considered for this purpose. Numerical results for the semisubmersible motion response in extreme hurricane and loop current are presented in this paper. The paper also compares the FHSB Semi designs that support certain payload/number of risers in the GoM, in the North West Shelf Australia and in Brazil. Key figures from this comparison are presented in the paper. The paper includes discussions on the proposed project execution plan covering the fabrication, transportation and installation as well as the added risks and risk mitigations associated with the new semisubmersible design and execution.
The Tension Leg Semisubmersible (TLS) floater is the second generation of the Free-Hanging Solid Ballast Semisubmersible (FHSB Semi) design. The FHSB Semi is the state-of-the-art design that maintains the advantages of the conventional Semisubmersibles and provides the motions of Spars. The FHSB Semi design is a conventional semisubmersible with an added feature of a Free-Hanging Solid Ballast tank (SBT) located deep below the hull keel level and connected through four groups of chains (on its four corners) to the semisubmersible hull. During the pre-service conditions, the chains are used to retract the SBT and maintain it at a close proximity to the hull keel to facilitate the transportation and installation operations. Once the semisubmersible is moored in-place, the chain system is operated to lower the SBT to its desired elevation below the hull keel and maintain it permanently connected to the semisubmersible hull during the in-service condition. The SBT provides substantial in-water weight and added mass that significantly reduce the platform response and maintains the chains in tension.
In this paper, detailed description of the Tension Leg Semisubmersible (TLS) design as the second generation of the FHSB Semi is presented. The paper also includes discussions on the proposed project execution plan for the TLS covering the fabrication, transportation and installation as well as the added risks and risk mitigations associated with the new semisubmersible design and execution.
A case study is introduced where a TLS is used as a dry tree host for a field located at 6,000 ft of water in the central Gulf of Mexico (GoM) harsh environment.
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