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Creatine kinase (CK) primarily serves as an energy buffer assisting in regulating ATP homeostasis through synthesis of ATP from ADP and phosphocreatine (PCr). This enzyme is bound in the sarcomere near sites of ATP consumption via acto-myosin ATPase (A‧M‧ATPase) and research in cardiac muscle has found that PCr can alter contractile performance (maximal isometric force and Ca²⁺ sensitivity). Based on this evidence, CK and A‧M‧ATPase may be coupled in skeletal muscle. Therefore the purpose of this investigation was to determine the influence of the CK system on contractile performance and energy utilization in skeletal muscle. When skinned fibers (membrane removed) were provided a limited supply of [ATP] (0.1 mM), this resulted in increased Ca²⁺ sensitivity. The addition of PCr to low ATP solutions restored Ca²⁺ sensitivity and allowed normal isometric force generation across a range of [Ca²⁺] via ATP synthesis by CK. This was also possible with only CK reaction substrates (ADP, PCr) in the absence of ATP. Based on these findings, endogenous CK activity in glycerol skinned skeletal muscle fibers is sufficient to permit normal function of the contractile apparatus. Energy utilization was studied by indirect assessment of ADP production. Decreased net ADP production as measured by NADH fluorescence revealed endogenous CK was able to convert ADP produced by A‧M‧ATPase to ATP in skeletal muscle across a range of both [Ca²⁺] and [ATP]. This was confirmed directly via high-performance liquid chromatography measurements of ATP and ADP by showing that skinned skeletal muscle bundles have sufficient endogenous CK activity to produce ATP from substrates (ADP, PCr) and the ability to maintain low [ADP] in the presence of PCr. This study adds to the evidence for specific compartmentation of CK near sites of ATP utilization and contributes to the body of knowledge on contractile performance in skinned skeletal muscle fibers. By showing how changing demands on skeletal muscle (through increased Ca²⁺) alters force production and Ca²⁺ sensitivity, these findings lend support for the importance of endogenous CK as a pathway of ATP regeneration in skeletal muscle. / Ph. D.

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In the field of energetics, much effort is focused on the development of safe, high performance energetic materials for use in military and civilian sectors. An effective explosive must possess good energetic properties such as high energy density, detonation velocity, and detonation pressure. Such materials must also be insensitive to physical initiation stimuli such as impact, friction, electrostatic discharge, and heat to allow for the safe synthesis, transportation and storage of the energetic material. To develop explosives with both high performance and safety metrics, this work seeks to create novel high-energy density energetic materials with controllable sensitivities. An improvement in energy density is obtained through linkage of energetic organic salts to transition metals, which breaks the ionic network of the salt and allows for more energy release upon combustion. Thermal sensitivity modulation is achieved by use of a magnetic field to stabilize a hexanuclear manganese cluster and increase its initiation temperature by 10.4 ± 3.9 °C. Furthermore, nitrotetrazole ligands were used to synthesize novel energetic coordination polymers with good oxygen balance. These complexes were studied with magnetometry experiments to probe the use of these materials as magnetically switchable explosives. Lastly, methylammonium salts were investigated for use as bridging ligands to create high-energy density clusters. / Chemistry