Development of catalytic enantioselective boron conjugate addition reaction to unsaturated compounds with copper-phosphine complexes and Zinc-catalyzed enantioselective hydrosilylation of imines

Feng, Xinhui Sungkyunkwan Univercity 2012 국내박사

Herein, we describe our results on the enantioselective β-boration of α,β-unsaturated carbonyl compounds including acyclic enones, cyclic enones, lactones and β, β-disubstituted α,β-unsaturated esters by using chiral diphosphine copper complexes. We also investigated a copper-catalyzed highly regio- and enantioselective hydrboration for the preparation of 1,1-diborylalkanes by using DTBM-Segphos or Josiphos ligand and pinacolborane as the borane source. The β-boryl (Bdan) substituted of substrate as a mask group is remarkably effective for reactions. In particular, the chiral center is retened after homologation of the substrate. An improved procedure for the asymmetric hydrosilylation of imines by using polymethylhydrosiloxane (PMHS) and chiral diamine-zinc complexes is developed. A series of chiral diamine ligands were prepared from optically pure 1,2-diphenyl-1,2-ethanediamine and screened for effectiveness. N-Benzylic substituents were required for high enantioselectivity and ligands with bulky groups or extra coordinating groups such as OH and S lowered the catalytic activity. The level of asymmetric induction was usually in >90% ee range for aromatic imine substrates.

Electrical characteristics of inkjet-printed organic thin film transistors (OTFTs) with blended organic semiconducting inks

Ko, Jung Min Sungkyunkwan Univercity 2012 국내박사

The blending of crystalline organic semiconductor, 6,13-bis(triisopropylsilylethynyl)-pentacene (TIPS pentacene) with amorphous polymers exhibits not only excellent solution processibility but also superior performance characteristics in organic thin film transistors (OTFTs). To understand the inkjet printing behavior of TIPS pentacene/polymer blends, we synthesized triarylamine-based polymers with various polarities, which were obtained by changing the fluorine content in the polymer structure. The variation of segregation strength of the polymer domains in the blends can be induced depending on the different polarities of the polymers, which can ultimately determine the shape and orientation of the TIPS pentacene crystals in OTFT films. The experimental results suggest that the phase separation behavior between the polymer and TIPS pentacene plays a significant role in the formation of crystal structure of TIPS pentacene in the film. The moderate segregation of the polymers from the TIPS pentacene crystal domains effectively derives the desirable stripe-shaped crystals with the proper orientation and enhanced surface morphology. The resultant inkjet-printed films from the triarlyamine-based polymers with TIPS pentacene showed excellent mobility of 0.14 to 0.19 cm2V-1s-1. Also, we use amorphous polycarbonate (APC), which is structurally beneficial to the facile phase separation with TIPS pentacene crystals due to its highly amorphous character. The various inkjet-printing behaviors of TIPS pentacene/APC inks that depend on the TIPS pentacene/APC compositions, ink viscosities, and different solvent mixtures are investigated, which can ultimately determine the phase separation, morphology, shape, and orientation of the TIPS pentacene crystals in OTFT films. Flory-Huggins phase separation theory is applied and various analytical methods such as polarized optical microscopy, 3D surface profile, and time-of-flight secondary ion mass spectroscopy (TOF-SIMS) are utilized to explain these relationships. By controlling these inkjet-printing conditions, it is possible to easily regulate the optimal inkjet-printing process for TIPS pentacene/polymer systems, which can derive the desirable stripe-shaped and vertically phase-separated TIPS pentacene crystals with the proper orientation and enhanced surface morphology. The resultant inkjet-printed films from the TIPS pentacene with APC show excellent device stability and an average mobility of 0.53 cm2V-1s-1, which are among the highest values obtained by inkjet-printing reported to date. Furthermore, the inkjet-printed flexible OTFT array with an average mobility of 0.27 cm2V-1s-1 sustains the application of TIPS pentacene/ APC in the field of flexible printed electronics. 유기반도체 (6,13-bis(triisopropylsilylethynyl)-pentacene (TIPS pentacene))와 무정형 고분자가 혼합된 유기반도체 잉크는 뛰어난 용액공정성과 우수한 트랜지스터 특성을 나타낸다. 본 연구에서는 다양한 조건으로 혼합된 유기 반도체/고분자 잉크를 사용하여 잉크젯 프린팅 공정에서 팁스 펜타센과 무정형 고분자가 혼합된 유기반도체 잉크의 거동을 이해하고, 제어함으로써 잉크젯 프린팅 공정으로 제작된 유기 박막 트랜지스터의 전기적 특성을 향상시키는 연구를 수행하였다. 먼저 정공 전달 구조인 triarylamine 구조를 바탕으로 하고 불소의 함량이 틀린 고분자를 합성하였다. 합성된 고분자는 고분자 구조내의 불소의 함량에 따라서 다양한 극성을 나타내었다. 합성된 고분자의 다양한 극성은 유기반도체와 고분자간의 상 분리의 상이함을 야기시키게 되고 팁스 펜타센/고분자 유기 박막내에서 팁스 펜타센의 결정 모양과 결정 배향성 및 박막 거칠기에 영향을 준다. 이는 궁극적으로 유기 박막 트랜지스터 소자의 전기적 특성을 좌우하게 된다. 실험을 통해서 팁스 펜타센과 고분자의 상 분리 거동이 박막내에서 팁스 펜타센 결정 구조의 형성에 중요한 역할을 하고, 팁스 펜타센 결정영역으로부터 적절하게 분리된 고분자의 상분리는 유기반도체 결정의 배향성을 증가시키고 표면 거칠기를 부드럽게 하여 효과적으로 줄무늬 형태의 결정을 형성하는데 도움을 준다. 결과적으로 triarylamine을 바탕으로 합성한 고분자와 팁스 펜타센을 유기 반도체 잉크로 이용하고 잉크젯 프린팅 공정으로 제작된 유기박막트랜지스터는 우수한 전하이동도 (0.14 ~ 0.19 cm2V-1s-1) 특성을 나타내었다. 또한 무정형 특성이 강하고 팁스 펜타센 결정의 상 분리 특성에 고분자 구조적으로 강점이 있는 폴리카보네이트 (APC) 고분자를 이용하여 다양한 조건(혼합용액 조성비, 잉크 점도 및 용매 변화)에서 혼합 잉크를 제작하였고, 이를 사용하여 잉크젯 프린팅 공정으로 제작된 유기박막트랜지스터의 특성 변화를 분석하였다. 조건에 따라서 유기박막트랜지스터 박막내의 결정 상 분리, 박막 거칠기 및 결정 모양과 배향 정도의 상이함을 polarized optical microscopy, 3D surface profile와 TOF-SIMS 장비를 이용하여 분석하였고, 결과를 플러리-허긴스 상분리 이론에 적용하여 설명하였다. 이러한 잉크젯 프린팅 조건을 최적화하여 팁스 펜타센과 APC 고분자간의 적절한 상분리를 유도함으로써 유기 반도체의 결정형성 특성 및 박막의 표면 거칠기를 향상시켜 0.53 cm2V-1s-1의 우수한 전하이동도를 갖는 유기 박막 트랜지스터 소자를 제작하였다. 또한 유연한 기판위에 0.27 cm2V-1s-1의 전하이동도를 갖는 유기 박막 트랜지스터 소자를 제작하여 향후 플렉시블 차세대 디스플레이 소재로서 적용 가능함을 제시하였다.

Evaluation of anti-diabetic effects of novel PTP1B inhibitors isolated from stereocaulon alpinum

Gwon, A-Ryeong Sungkyunkwan Univercity 2012 국내박사

Diabetes mellitus is a chronic metabolic disorder that is caused by a failure of the body to produce insulin and/or an inability of the body to respond adequately to circulating insulin. Type 2 diabetes, previously called non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes, accounts for 90-95% of diagnosed diabetes cases worldwide. Type 2 diabetes is characterised by resistance to hormones insulin, possibly due to attenuated or diminished signalling from the receptors. Pharmacological agents capable of inhibiting the negative regulator(s) of the signalling pathways are expected to potentiate the action of insulin and therefore be beneficial for the treatment of Type 2 diabetes. Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator of insulin signalling. In addition, evidence suggests that insulin action can be enhanced by the inhibition of PTP1B; however, targeting PTP1B for drug discover is challenging because of the highly conserved and positively charged active-site pocket. The insulin-antagonizing activity of PTP1B has been demonstrated by a number of biochemical and genetic studies. In this study, we evaluated anti-diabetic effects of isolated metabolite, natural product Lobaric acid from Antartic lichen Stereocaulon alpinum and its directly derived compound M11 and M11A. To investigate the action of putative PTP1B inhibitor, we first tested whether M11A increase the phosphorylation of insulin receptor (IR) and insulin receptor substrate (IRS). Treatments of M11A inreased the phosphorylation level of IR and IRS. Treatment of diabetic and obese mice with this compound resulted in normalization of hyperglycemia, restoration of systemic insulin sensitivity, and enhancement of insulin action in liver tissue. Our results demonstrate that Lobaric aicd, M11 and M11A acts as potent antidiabetic modality with potential application in the treatment of type 2 diabetes.

Formulation of dual release fixed-dose combination tablet for treatment of diabetes

Kim, Dong-Wook Sungkyunkwan Univercity 2012 국내박사

The aim of the present study was to formulate new fixed-dose combination tablets by coating a glimepiride immediate-release layer on a metformin hydrochloride sustained-release core tablet using perforated film coating equipment. Composition of glimepiride immediate-release coating suspension for homogeneity was studied and application of near infrared spectroscopy (NIR) to determine the end-point of the coating process was also investigated. The final product was administered to healthy male volunteers and its pharmacokinetic parameters were analyzed. Glimepiride immediate-release coating suspension was prepared with a ratio of sodium lauryl sulfate to glimepiride at 0.75 for homogeneity. An inert mid-layer was introduced to prevent contact between metformin hydrochloride sustained-release core tablet and glimepiride immediate-release coating layer, which led to an increased release rate of glimepiride in pH 7.8 medium. The proportional correlation was confirmed between analytical results of glimepiride determined by validated NIR method and those by HPLC-UV. Thus, the end-point of the glimepiride coating process was determined by NIRS, the fast and non-destructive method. The coating process was optimized by design of experiment. Novel dual release fixed dose combination tablet was confirmed to be bioequivalent to the marketed product.

Study on the modified bulk-FinFETs for DRAM cell transistor

Kim, Keunnam Sungkyunkwan Univercity 2012 국내박사

DRAM 기술이 선 폭 50nm 이하 수준으로 접어들면서, DRAM 셀 (Cell) 소자의 특성을 확보하기가 점점 더 어려워지고 있다. 특히, 소자를 축소시키면서 오프 상태(Off-state) 누설전류는 증가하고 온 상태 (On-state) 구동전류는 감소하여 전하 보존 특성 (Retention time)을 더욱 더 취약해졌다. 이를 개선하기 위하여, FinFET 구조에 대한 연구가 활발히 진행되고 있다. FinFET은 얇은 바디 (thin body) 구조이기 때문에 짧은 채널 효과 (short channel effect)를 개선하기 용이하고, 채널 조정성 (controllability)이 뛰어나다. 이런 장점에도 불구하고, 기존 형태의 FinFET은 문턱 전압 (threshold voltage)를 조절하기가 어렵고, 게이트 산화막 형성 시 소스/드레인 (source/drain) 영역까지 산화되어 접촉 면적이 줄어드는 단점이 있다. 본 연구에서는 기존 FinFET 구조가 가지고 있는 문제를 해결하기 위하여 세 가지 FinFET 구조를 제안하고, 각각의 소자를 제작하였으며 그 특성을 평가하였다. 개선된 세 가지 구조는 (1) 다마신 (Damascene) 게이트 구조를 가진 FinFET (Damascene FinFET, D-FinFET), (2) 패스 (pass) 게이트 교란 (disturbance)을 방지하기 위하여, 패스 게이트에는 다마신을 적용하지 않은 구조를 갖는 FinFET (Local Damascene FinFET, LD-FinFET), (3) FinFET의 문턱 전압을 조절하고, 짧은 채널 효과를 개선하기 위하여 필드 (Field) 영역 뿐만 아니라 실리콘 기판 (Active)까지 리세스 (Recess)한 구조를 갖는 FinFET (Recessed Channel FinFET, R-FinFET) 이다. 이 세 구조는 기존 FinFET의 특성을 개선함으로써. 50nm 이하의 선 폭을 가지는 DRAM에서도 집적도와 전하 보존 특성을 증대시킬 것으로 예상된다. D-FinFET 공정을 이용하여 세계 최초로 FinFET 셀 구조를 가진 DRAM을 제작하여 동작시켰다. 기존 구조 FinFET 대비 D-FinFET에서 접촉저항이 60% 개선되었다. 접촉저항이 개선된 이유는 게이트 산화막 공정 시 소스/드레인 영역이 산화되는 것을 방지하여 접촉면적을 보존하였기 때문이다. 이로 인해 온 상태 구동전류는 10% 증가하였다. 또한, 3차원 시뮬레이션으로 D-FinFET에 적합한 도핑 (doping) 조건을 찾아서 적용하였다. 그 결과 접합 누설 전류와 전하 보존 특성을 개선하였다. D-FinFET에서 여러 가지 특성이 개선되었지만, D-FinFET은 패스 게이트 교란 (pass gate disturbance) 문제를 가지고 있었다. 패스 게이트 교란 효과는 게이트 유도 드레인 누설전류 (Gate-induced drain leakage,GIDL) 및 문턱 전압 강하를 야기하여 DRAM의 전하 보존 특성을 저하시켰다. 이를 개선하기 위하여 LD-FinFET이 개발되었다. D-FinFET에서는 다마신 패턴을 패스 (pass)와 어세스 (access) 게이트 아래 모든 영역에 형성하였는데, LD-FinFET에서는 채널이 형성될 어세스 게이트에만 형성하여 패스 게이트 교란 효과를 제거할 수 있었다. LD-FinFET은 두 가지 공정으로 제작되었으며 이것을 자세히 설명하였다. 추가로, 기판 바이어스 (bias)가 GIDL에 미치는 영향도 LD-FinFET 구조로 연구하였다. 수평 방향 전계가 핀 (fin)의 공핍 영역에 의해 차폐된다는 것을 확인하였고, 세 단자 GIDL 모델로 설명하였다. 마지막으로, FinFET의 특성을 잘 이해하기 위하여 시뮬레이션을 진행하였다. 이를 통해 FinFET의 오프 상태 누설전류가 핀 꼭대기로부터 20~30nm 아래 영역에서 대부분 발생한다는 것을 알아내었다. 만약 이 누설전류의 통로를 제거하면 FinFET의 누설 전류가 개선될 뿐만 아니라 문턱전압도 조절될 수 있다는 것을 예측하였다. 누설전류의 통로는 엑티브 (Active) 실리콘을 리세스하여 제거하였고, 이 FinFET을 R-FinFET (Recessed Channel FinFET)이라고 명명하였다. 실리콘을 리세스하여 유효 채널 길이를 증가시켰기 때문에 R-FinFET은 짧은 채널 효과가 개선되었으며, 문턱전압이 상승하였고, 오프 상태 및 GIDL 누설전류가 삭감되었다. 또한 전기적 특성도 개선되었는데, 드레인 유도 소스 장벽 감소 (Drain-induced barrier lowering, DIBL)은 20mV/V, 문턱 전압아래 기울기 (sub-threshold slope)는 89mV/dec, 기판 바이어스 효과 (body bias effect)는 190mV/V를 나타낸다. 또한, R-FinFET의 전기적 특성을 세 소자 직렬 연결 (three series-connected transistors) 모델을 제안하여 성공적으로 설명하였다. 결론적으로, 기존 FinFET보다 개선된 구조를 갖는 FinFET이 DRAM 셀 소자에 적용되면, 소자의 축소 한계를 극복할 수 있음을 확인하였다.

Ultrasensitive biosensing by organic and graphene based transistors for disease diagnosis

Kim, Duck-Jin Sungkyunkwan Univercity 2012 국내박사

Detection of specific protein biomarkers are extremely urgent issue for disease diagnosis and monitoring. Many studies have been developed various signal transducer based on optical, mechanical, electrochemical and electrical method. Recently, electrical detection of disease biomarkers is significantly studied to overcome the technical limitation of optical and mechanical detection method such as large instrumentation, long analysis time, and constraints of nanofabrication. The biosensor require the high sensitivity, high specificity, high stability, low limit of detection, wide dynamic range, real-time detection, simple fabrication for the realization of the point-of-care (POC) disease diagnostic system as well as biological study of proteomics and cellomics. To achieve this requirement, the development of transducing materials, recognition receptors with high affinity and high dense immobilization method are necessary. Here, the suggested different strategies and devices for the improvement of detection sensitivity based on organic material and graphene based transistors enabling the minimum quantification of various biomarkers. This thesis is divided into three experimental part where 1) organic electrochemical transistor (OECT) with conjugated polymer for detection of prostate specific antigen/α1-antichymotrypsin (PSA-ACT) complex combined with the signal amplification by gold nanoparticle; 2) reduced graphene oxide field effect transistor (RGO-FET) for detection of PSA-ACT complex; 3) aptamer modified RGO-FET for detection of protective antigen (PA) in anthrax with signal amplification. The first purpose of this thesis was that the first development of OECT immunosensor for detection of cancer biomarker. The conjugated polymer, poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS), was applied to the detection of cancer biomarker with the secondary PSA polyclonal antibody conjugated gold nanoparticle (PSA pAb-AuNP) for signal amplification. The calixcrown based self-assembled monolayer (SAMs) for the linker molecule was selectively functionalized on the aminated PEDOT:PSS. The PSA mAb was immobilized on the PEDOT:PSS and then the sensing characteristics was obtained varying by the concentration of PSA-ACT complex in PBS solution. The second purpose of this thesis was that the first development of highly sensitive reduced graphene oxide field-effect transistor (RGO-FET) for detection of cancer biomarker. The ultrathin nature and large reactive area of graphene induced the very sensitive response to biomolecule. The scalable and facile fabrication of RGO-FET have the capability of label-free, ultrasensitive electrical detection of a cancer biomarker, PSA-ACT complex, in which the ultrathin R-GO channel was formed by a uniform self-assembly of two-dimensional RGO nanosheets. The third purpose of this thesis was that the enhancement of RGO-FET performance by aptamer as recognition receptor and signal amplification by gold nanoparticle. In this experiment, the RGO-FET was applied to the detection of anthrax exotoxin, i.e. protective antigen (PA). This study demonstrates the Debye screening effect, which are critical issue in electrical sensor, varying by the concentration of PBS solution. The use of aptamer for the RGO-FET provide the one way to overcome the Debye screening as well as the highly dense immobilization due to comparably small size. And the signal amplification was achieved by the aptamer conjugated gold nanoparticle for the realization of very ultrahigh sensitive biosensor. These results indicated that I have successfully developed and exploited OECT and RGO-FET based biosensor that enable the detection of biomolecules with ultralow limit of detection (LOD), high sensitivity, and wide dynamic range. These organic material and graphene based biosensor is good candidate for the early diagnosis of disease as well as biological studies.