Interaction Energy Analysis for Drug-Cyclodextrin Inclusion Complexes in Aqueous Solutions

It is vital to elucidate the role of asymmetric intermolecular interactions resulting from the stereospecific structures of molecules in order to understand the mechanisms of chemical and biochemical reactions such as enzyme-substrate reactions, antigen-antibody reactions, etc. In order to reveal the mechanism of the inclusion phenomenon for b-cyclodextrin (CD)-ampicillin complexes and b-CD-ibuprofen complexes, binding free energies were determined using molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) analysis. To clarify the details of the interaction energies of these complexes, pair interaction energy decomposition analysis (PIEDA) was carried out. The direction of inclusion of drugs into b-CD cavities was clarified on the basis of results obtained using the above-mentioned methods

Fully automated synthesis and purification of 4-(2\u27-methoxyphenyl)-1-[2\u27-(N-2\u27\u27-pyridinyl)- p-[18F]fluorobenzamido]ethylpiperazine

We have developed an efficient synthesis method for the rapid and high-yield automated synthesis of 4-(2\u27-methoxyphenyl)-1-[2\u27-(N-2"-pyridinyl)-p-[18F]fluorobenzamido]ethylpiperazine (p-[18F]MPPF). No-carrier-added [18F]F1 was trapped on a smallQMA cartridge and eluted with 70% MeCN(aq) (0.4 mL) containing Kryptofix 222 (2.3 mg) and K2CO3 (0.7 mg). The nucleophilic[18F]fluorination was performed with 3mg of the nitro-precursor in DMSO (0.4 mL) at 190 C for 20 min, followed by thepreparative HPLC purification (column: COSMOSIL Cholester, Nacalai Tesque, Kyoto, Japan; mobile phase: MeCN/25mMAcONH4/AcOH = 200/300/0.15; flow rate: 6.0 mL/min) to afford p-[18F]MPPF (retention time = 9.5 min). p-[18F]MPPF wasobtained automatically with a radiochemical yield of 38.6 5.0% (decay corrected, n = 5), a specific activity of 214.3 21.1GBq/mmol, and a radiochemical purity of >99% within a total synthesis time of about 55 min

High-yield automated synthesis of[18F]fluoroazomycin arabinoside([18F]FAZA) for hypoxia-specific tumor imaging

The aimofthisstudywastodevelopanefficientfullyautomatedsynthesismethodtoachieveahighradiochemicalyieldof[18F]FAZA withasmallamountofprecursor.Asmallcartridgecontaining25mgoftheQMAresinwaspreparedandevaluatedtoobtain[18F]F1 in asmallquantityofbase(K2CO3), whichmight allowtheuseofasmallamountofprecursor. Thelabelingandhydrolyzingconditionsfor[18F]FAZAsynthesiswerealsoinvestigatedmanually.No-carrier-added[18F]F1 was trappedonthesmallQMAcartridgeandelutedwithamixtureofKrytofix222(2.26mg,6.0 mmol)andK2CO3 (0.69 mg,5.0 mmol)in70%MeCN(0.4mL).Theautomatedsynthesisof[18F]FAZA wasoptimallyperformedwithamodifiedNIRSoriginalsynthesissystemforclinicaluse,bylabeling2.5mg(5.2 mmol)oftheprecursorinDMSO(0.4mL)at120 1C for10min,andthenbyhydrolyzingthe 18F-labeledintermediatewith0.1MNaOH(0.5mL)atroomtemperaturefor3min.Usingtheabovecondition,the[18F]FAZAinjectionwasobtainedwithahighradiochemicalyieldof52.475.3%(decay-corrected, n¼8) within50.571.5min