Name: amide coupling reaction for the synthesis of bispyridine-based ligands and their complexation to platinum as dinuclear anticancer agents
Uploaded: 2014-05-28T14:00:00.000+00:00
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Description: Watch this Scientific Journal Video about Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents at JoVE.com

1 N, N &#39;의 합성 -. (알칸-1, N-디일) diisonicotinamide <ol><li> 모든 수분을 제거하기 위해 오븐 (100 º C, 1 시간)에서 하나의 목 또는 3 구 둥근 바닥 플라스크를 건조. </li><li> 자기 교반 막대와 함께 플라스크에 고체 이소 니코틴산, 또는 그 유도체를 추가합니다. diaminoalkane 리간드 (들)이 실온에서 고체 인 경우에, (이소 니코틴산의 숫자 몰) 0.5 몰의이 단계에서 플라스크에 첨가된다. </li><li> 고무 격막으로 플라스크의 목 (들) 모자 및 지속적인 질소 스트림을 통해 또는 질소 채워진 풍선의 사용을 통해 하나의 질소와 함께 플라스크 내에서 공기를 교체한다. </li><li> 고체를 용해 무수 디메틸 포름 아미드 또는 디메틸 술폭 시드 (아이소 니코틴산 또는 2 - 메틸 - 아이소 니코틴산 500 mg의 당 4 ㎖)에 추가하는 피하 주사 바늘 및 주사기를 사용한다. 고형물이 쉽게 용해되지 않는 경우, 상기 용액을 온화하게 가열한다. </li><li> 에 7 몰 당량 (추가트리 에틸 아민 (약 염기)과 diaminoalkane 0.5 몰 당량 사용되는 이소 니코틴산)의 산. 용액은 실온에서 액체 인 경우, 1.5 몰 당량을 추가한다. </li><li> 연속 교반하면서 1 - 프로필 포스 무수물 (커플 링제)의 1 몰 상당을 추가하고 반응이 5-12 시간에 완료 할 수 있습니다. </li></ol> 리간드 2. 정제 <ol><li> 반응이 진행됨에 따라 제품이 용액으로부터 침전에 10 개 이상의 메틸렌 그룹과 diaminoalkane 리간드를 사용하여 만든 비스 피리딘 리간드를 들어, 기다립니다. </li><li> 비스 피리딘 리간드 디아를 사용하여 제조를 들어, ~에게 물 40 ㎖를 첨가하여 생성물을 침전. </li><li> 비스 피리딘은 2-6 메틸렌 그룹의 디아 미노를 사용하여 만든 경우, 물 ~ 40 ㎖를 추가하고 화합물 1-3 일에 걸쳐 구체화 할 수 있습니다. </li><li> 진공 여과에 의해 각 비스 피리딘 리간드를 수집하고 당 200 끓는 물에 약 400 ~ 500 ㎖의 재결정리간드의 MG. 참고 : 더 많은 물이 그들의 환원수 용해도로 인해 긴 비스 피리딘 리간드 필요하다. </li><li> 화합물은 재결정시 무료 기지를 보장하기 위해 솔루션의 NaOH 및 KOH (pH가 9)를 추가합니다. </li></ol> 이핵 플래티넘 단지 3. 합성 및 정제 <ol><li> 완전 (II), transplatin은, 뜨거운 (70 ~ 80 º C에서) 물 (transplatin 200 밀리그램 당 150 ㎖)을 분명 강하게 노란색 컬러 솔루션을 생산하는 트랜스 diamminodichloridoplatinum을 녹입니다. </li><li> 비스 피리딘 리간드의 0.5 몰 상당을 추가하고 리간드 해소 (맑은 용액)까지의 온도에서 저어. 무색 근처에 설정하는 솔루션을 기다립니다 열을 끄고, 몇 가지 추가 시간 동안 실온에서 교반. </li><li> 노란 색깔의 분말을 얻을 것이다, 회전 증발에 의해 용매를 제거합니다. </li><li> 최소 따뜻한 물 양 (~ 50 &amp;에 용해하여, 백금 착물 (들)를 정화# 186, C). 남아있는 노란색 또는 흰색 컬러 고체가있는 경우, 다음이를 필터링 할 수 있습니다. </li><li> 금속 착체의 중합체 형태로 나타나며, 반응 생성물의 10 %까지 나타내는 백색 침전물이 형성 될 때까지 용액에 아세톤을 추가. 더 이상 침전물이 나타납니다 때까지 아세톤을 첨가 (~ 추가로 20 ~ 30 ㎖)을 계속합니다. 참고 :이 흰색 침전물이 불순물이다. </li><li> 나일론 여과지 (0.2 ㎛의 공극 크기) 및 순수한 생성물을 수득 할 건고 잔류 용액을 회전 증발을 통해 내용물을 여과하여 침전물을 제거한다. 주 : 필요한 경우, 추가의 아세톤 침전 단계가 복잡 순정까지 수행 될 수있다. </li></ol>

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저자가 공개하는 게 없다.

이 작품에서 이핵 백금 착물은 잠재적 인 항암제로 합성되었다. 이렇게 제조 된 비스 피리딘 가교 리간드 이소 니코틴산 및 가변 길이 디아 미노 알칸을 사용 아미드 커플 링 반응을 통해 합성 하였다. 이전에 2 ~ 8 메틸렌 그룹과 각각의 백금 착체와 비스 피리딘 리간드와 자신의 메틸 유사체의 합성이보고 된 바있다. 본 논문에서는 합성 및 정제 방법은보다 빠르고 저렴하고 개정되었습니다, 8, 10,...

백금 항암제는 인간의 암 (1)의 치료에 에이전트의 가장 널리 사용되는 제품군 중 하나 남아있다. 자신의 성공에도 불구하고, 그들은 심각한 용량 제한 부작용 2-4으로 자신의 응용 프로그램에 제한됩니다. 환자에게 투여 할 수있는 제한 용량은 종양이 저항 5를 개발할 수 있다는 것을 의미한다. 예컨대, 새로운 약물 부작용 프로파일을 개선하고 phenanthriplatin 6 및 7 phosphaplatin 같이 취득한 저항을 극복하기 위해 개발 될 계속. 1990 년대 후반, trinuclear 백금 약물, BBR3464 (반응식 1) 8, 즉 최고의 백금 약물, 시스플라틴보다 체외에서 최대 1,000 X 더 많은 세포 독성을 개발했다. BBR3464 또한 인간 암 세포주 15의 패널에서 취득한 저항을 극복 할 수있다. 불행하게도, BBR3464의 증가 된 활동은 50 일치 - 100 - 높은 독성을 배하는10-12의 사용을 제한합니다. 그것은 또한 쉽게 ​​약물의 작은 의미, 몸에서 분해되어 9 그대로 암 핵에 도달한다. Picoplatin는 2 - 메틸 - 피리딘 리간드 (반응식 1) (13)를 포함 단핵 백금 계 약물이다. 본제의 메틸기 생물학적 친핵체에 의한 공격으로부터 보호; 특히 시스테인 및 펩타이드 / 단백질 14 ~ 16가 포함 된 메티오닌. 이와 같이, 약물은 매우 안정되어 BBR3464 및 시스플라틴 (17) 모두와 비교하여 암 핵 도달 훨씬 높은 농도를 갖는다. 그 감소 된 반응성도 picoplatin가 BBR3464 및 시스플라틴 10,18,19에 비해 높은 최대 허용 선량을 의미합니다. 이 프로젝트는 따라서 개선 된 생물학적 안정성과 덜 심각한 측면 EFFE을 표시 인수 저항을 극복 할 수있는 새로운 약물을 생산하기 위해 BBR3464 및 picoplatin의 속성을 결합하는 노력CTS (예를 들어, 그림 1). 이 과정에서, 이핵 백금 착체의 범위는 가교 된 비스 피리딘 리간드와 20을 제조 하였다. 리간드 아이소 니코틴산 또는 2 - 메틸 - 아이소 니코틴산, 가변 길이 디아 미노 알칸 같은 그 유도체와의 아미드 커플 링 반응을 사용하여 제조된다. transplatin 두 몰 당량 리간드의 1 몰 상당의 반응은 원하는 백금 착물 (반응식 1)를 산출한다.

<table><tbody><tr><td>D&lt;sub&gt;2&lt;/sub&gt;O</td><td>Aldrich</td><td>151882</td><td>99.9% D</td></tr><tr><td>DMSO-d&lt;sub&gt;6&lt;/sub&gt;</td><td>Aldrich</td><td>156914</td><td>99.96% D</td></tr><tr><td>1,8-diaminooctane</td><td>Aldrich</td><td>D22401</td><td>98%</td></tr><tr><td>1,10-diaminodecane</td><td>Aldrich</td><td>D14204</td><td>98%</td></tr><tr><td>1,12-diaminododecane</td><td>Aldrich</td><td>D1,640-1</td><td>98%</td></tr><tr><td>Isonicotinic acid</td><td>Aldrich</td><td>I17508</td><td>99%</td></tr><tr><td>1-Propylphosphonic anhydride solution</td><td>Aldrich</td><td>431303</td><td>50 wt% in ethyl acetate</td></tr><tr><td>Trans-diaminodichloridoplatinum(II)</td><td>Aldrich</td><td>P1525</td><td></td></tr><tr><td>Dimethylsulfoxide</td><td>Sigma-Aldrich</td><td>Z76855</td><td>&gt;99.9%, anhydrous</td></tr><tr><td>&lt;em&gt;N,N&amp;rsquo;&lt;/em&gt;-dimethylformamide</td><td>Sigma-Aldrich</td><td>227056</td><td>99.8%, anhydrous</td></tr><tr><td>Triethylamine</td><td>Sigma-Aldrich</td><td>T0886</td><td>&gt;99%</td></tr><tr><td>Nylon filter membranes</td><td>Whatman</td><td>7402-004</td><td>Pore size, 0.2 &amp;micro;m</td></tr><tr><td>Magnetic stirring hotplate</td><td></td><td></td><td></td></tr><tr><td>Magnetic stirring bar&amp;nbsp;</td><td></td><td></td><td></td></tr><tr><td>Round bottom or three neck flask</td><td></td><td></td><td></td></tr><tr><td>Rubber septums of sufficient size for chosen round bottom or three neck flask</td><td></td><td></td><td></td></tr><tr><td>5 ml hypodermic syringes</td><td></td><td></td><td></td></tr><tr><td>Hypodermic needles</td><td></td><td></td><td></td></tr><tr><td>Rubber party ballons</td><td></td><td></td><td></td></tr><tr><td>Rubber bands</td><td></td><td></td><td></td></tr><tr><td>A source of N&lt;sub&gt;2&lt;/sub&gt; gas</td><td></td><td></td><td></td></tr><tr><td>Rotary evaporator</td><td></td><td></td><td></td></tr><tr><td>Drying oven</td><td></td><td></td><td></td></tr><tr><td>NMR tubes</td><td></td><td></td><td></td></tr><tr><td>NMR spectrometer</td><td></td><td></td><td></td></tr><tr><td>500 ml beakers</td><td></td><td></td><td></td></tr><tr><td>Glass or plastic pipettes</td><td></td><td></td><td></td></tr></tbody></table>

amide coupling reaction for the synthesis of bispyridine-based ligands and their complexation to platinum as dinuclear anticancer agents

Amide coupling reactions can be used to synthesize bispyridine-based ligands for use as bridging linkers in multinuclear platinum anticancer drugs. Isonicotinic acid, or its derivatives, are coupled to variable length diaminoalkane chains under an inert atmosphere in anhydrous DMF or DMSO with the use of a weak base, triethylamine, and a coupling agent, 1-propylphosphonic anhydride. The products precipitate from solution upon formation or can be precipitated by the addition of water. If desired, the ligands can be further purified by recrystallization from hot water. Dinuclear platinum complex synthesis using the bispyridine ligands is done in hot water using transplatin. The most informative of the chemical characterization techniques to determine the structure and gross purity of both the bispyridine ligands and the final platinum complexes is 1H NMR with particular analysis of the aromatic region of the spectra (7-9 ppm). The platinum complexes have potential application as anticancer agents and the synthesis method can be modified to produce trinuclear and other multinuclear complexes with different hydrogen bonding functionality in the bridging ligand.

비스 피리딘 리간드와 각각 이핵 백금 착체 1 H, 13 C 및 195 편 NMR (표 1 및 2), 및 전기 분무 이온화 질량 분광법에 의해 특징된다. 정확한 융점은 최고의 C, H 및 N 함유율에 대한 원소 분석에 의해 측정되는 시차 주사 열량 및 순도를 사용하여 결정될 수있다. 그것이 결정적 성공 아미드 커플 링과 백금 조정 (표 1, 2)을 입증 할 수 공명과 ?...

Watch this Scientific Journal Video about Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents at JoVE.com

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

이 프로토콜은 항암제와 BBR3464 picoplatin의 양태를 결합 다핵 백금 착체의 합성에 사용하기에 적합한 가교 리간드를 형성하기 위해 이소 니코틴산 및 디아 미노 알칸의 아미드 커플 링 반응을 사용하는 방법을 설명한다.

이핵 항암제로 플래티넘 비스 피리딘 계 리간드와 이들 착물의 합성 아미드 커플 링 반응

Amide coupling reactions can be used to synthesize bispyridine-based ligands for use as bridging linkers in multinuclear platinum anticancer drugs. ...

amide-coupling-reaction-for-synthesis-bispyridine-based-ligands-their

Research

JoVE Journal

Chemistry

13.9K 조회수.  The University of Sydney.  이 프로토콜은 항암제와 BBR3464 picoplatin의 양태를 결합 다핵 백금 착체의 합성에 사용하기에 적합한 가교 리간드를 형성하기 위해 이소 니코틴산 및 디아 미노 알칸의 아미드 커플 링 반응을 사용하는 방법을 설명한다. 

비디오: Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

Anticancer Metal Complexes: Synthesis and Cytotoxicity Evaluation by the MTT Assay

Titanium (IV) and vanadium (V) complexes are highly potent anticancer agents. A challenge in their synthesis refers to their hydrolytic instability; therefore their preparation should be conducted under an inert atmosphere. Evaluation of the anticancer activity of these complexes can be achieved by the MTT assay.
The MTT assay is a colorimetric viability assay based on enzymatic reduction of the MTT molecule to formazan when it is exposed to viable cells. The outcome of the reduction is a color change of the MTT molecule. Absorbance measurements relative to a control determine the percentage of remaining viable cancer cells following their treatment with varying concentrations of a tested compound, which is translated to the compound anticancer activity and its IC50 values. The MTT assay is widely common in cytotoxicity studies due to its accuracy, rapidity, and relative simplicity.
Herein we present a detailed protocol for the synthesis of air sensitive metal based drugs and cell viability measurements, including preparation of the cell plates, incubation of the compounds with the cells, viability measurements using the MTT assay, and determination of IC50 values.

A method for synthesis of air-sensitive titanium and vanadium anticancer agents is described, along with the evaluation of their cytotoxic activity towards human cancer cell line by the MTT Assay.

MTT의 분석에 의해 합성 및 세포 독성 평가 : 항암 금속 합성물

Titanium (IV) and vanadium (V) complexes are highly potent anticancer agents. A challenge in their synthesis refers to their hydrolytic instability; ...

연구

화학

Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium Under Mild Reaction Conditions

Dichloro-bis(aminophosphine) complexes of palladium with the general formula of [(P{(NC5H10)3-n(C6H11)n})2Pd(Cl)2] (where n = 0-2), belong to a new family of easy accessible, very cheap, and air stable, but highly active and universally applicable C-C cross-coupling catalysts with an excellent functional group tolerance. Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium [(P(NC5H10)3)2Pd(Cl)2] (1), the least stable complex within this series towards protons; e.g. in the form of water, allows an eased nanoparticle formation and hence, proved to be the most active Heck catalyst within this series at 100 &#176;C and is a very rare example of an effective and versatile catalyst system that efficiently operates under mild reaction conditions. Rapid and complete catalyst degradation under work-up conditions into phosphonates, piperidinium salts and other, palladium-containing decomposition products assure an easy separation of the coupling products from catalyst and ligands. The facile, cheap, and rapid synthesis of 1,1',1"-(phosphinetriyl)tripiperidine and 1 respectively, the simple and convenient use as well as its excellent catalytic performance in the Heck reaction at 100 &#176;C make 1 to one of the most attractive and greenest Heck catalysts available.
We provide here the visualized protocols for the ligand and catalyst syntheses as well as the reaction protocol for Heck reactions performed at 10 mmol scale at 100 &#176;C and show that this catalyst is suitable for its use in organic syntheses.

Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions

Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium [(P(NC5H10)3)2Pd(Cl)2] (1) is an easy accessible, cheap, and air stable, but highly active Heck catalyst with an excellent functional group tolerance that efficiently operates under mild reaction conditions to give the coupling products in very high yields.

온화한 반응 조건 하에서 팔라듐 - 디클로로 {비스 [(phosphinetriyl) tripiperidine 1,1 &#39;, 1 &#39;&#39;]} 의해 촉매 Mizoroki-헥 크로스 커플 링 반응

Dichloro-bis(aminophosphine) complexes of palladium with the general formula of [(P{(NC5H10)3-n(C6H11)n})2Pd(Cl)2] (where n = 0-2), belong to a new family ...

The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphosPh Complexes

Herein we report the synthesis of a tridentate phosphine ligand N(CH2PPh2)3 (N-triphosPh) (1) via a phosphorus based Mannich reaction of the hydroxylmethylene phosphine precursor with ammonia in methanol under a nitrogen atmosphere. The N-triphosPh ligand precipitates from the solution after approximately 1 hr of reflux and can be isolated analytically pure via simple cannula filtration procedure under nitrogen. Reaction of the N-triphosPh ligand with [Ru3(CO)12] under reflux affords a deep red solution that show evolution of CO gas on ligand complexation. Orange crystals of the complex [Ru(CO)2{N(CH2PPh2)3}-&#954;3P] (2) were isolated on cooling to RT. The 31P{1H} NMR spectrum showed a characteristic single peak at lower frequency compared to the free ligand. Reaction of a toluene solution of complex 2 with oxygen resulted in the instantaneous precipitation of the carbonate complex [Ru(CO3)(CO){N(CH2PPh2)3}-&#954;3P] (3) as an air stable orange solid. Subsequent hydrogenation of 3 under 15 bar of hydrogen in a high-pressure reactor gave the dihydride complex [RuH2(CO){N(CH2PPh2)3}-&#954;3P] (4), which was fully characterized by X-ray crystallography and NMR spectroscopy. Complexes 3 and 4 are potentially useful catalyst precursors for a range of hydrogenation reactions, including biomass-derived products such as levulinic acid (LA). Complex 4 was found to cleanly react with LA in the presence of the proton source additive NH4PF6 to give [Ru(CO){N(CH2PPh2)3}-&#954;3P{CH3CO(CH2)2CO2H}-&#954;2O](PF6) (6).

The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphosPh Complexes

Ruthenium phosphine complexes are widely used for homogeneous catalytic reactions such as hydrogenations. The synthesis of a series of novel tridentate ruthenium complexes bearing the N-triphos ligand N(CH2PPh2)3 is reported. Additionally, the stoichiometric reaction of a dihydride Ru&#8211;N-triphos complex with levulinic acid is described.

루테늄의 시리즈의 합성, 특성 및 반응성<em&gt; N</em&gt; -triphos<sup&gt; 박사</sup&gt; 단지

Herein we report the synthesis of a tridentate phosphine ligand N(CH2PPh2)3 (N-triphosPh) (1) via a phosphorus based Mannich reaction of the ...

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from benzimidazolium salts. Detailed and generalized protocols are also presented for testing the catalytic activity of such complexes in arylation and Suzuki-Miyaura cross-coupling reactions. Representative results are shown for the catalytic activity of the four complexes in arylation and Suzuki-Miyaura type reactions. For each of the reactions investigated, at least one of the four complexes successfully catalyzed the reaction, qualifying them as promising candidates for catalysis of many carbon-carbon bond-forming reactions. The protocols presented are general enough to be adapted for the synthesis, purification and catalytic activity testing of new palladium N-heterocyclic carbene complexes.

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from benzimidazolium salts. The complexes were tested for catalytic activity in arylation and Suzuki-Miyaura reactions. For each reaction investigated, at least one of the four complexes successfully catalyzed the reaction.

보장<em&gt; N</em&gt; - 헤테로 사이 클릭 카벤 착물 : 벤즈 이미 다 졸리움 염으로부터의 합성 및 탄소 - 탄소 결합 형성 반응에서의 촉매 활성

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from ...

Preparation of SNS Cobalt(II) Pincer Model Complexes of Liver Alcohol Dehydrogenase

Chemical model complexes are prepared to represent the active site of an enzyme. In this protocol, a family of tridentate pincer ligand precursors (each possessing two sulfur and one nitrogen donor atom functionalities (SNS) and based on bis-imidazole or bis-triazole compounds) are metallated with CoCl2&#183;6H2O to afford tridentate SNS pincer cobalt(II) complexes. Preparation of the cobalt(II) model complexes for liver alcohol dehydrogenase is facile. Based on a quick color change upon adding the CoCl2&#183;6H2O to acetonitrile solution that contains the ligand precursor, the complex forms rapidly. Formation of the metal complex is complete after allowing the solution to reflux overnight. These cobalt(II) complexes serve as models for the zinc active site in liver alcohol dehydrogenase (LADH). The complexes are characterized using single crystal X-ray diffraction, electrospray mass spectrometry, ultra-violet visible spectroscopy, and elemental analysis. To accurately determine the structure of the complex, its single crystal structure must be determined. Single crystals of the complexes that are suitable for X-ray diffraction are then grown via slow vapor diffusion of diethyl ether into an acetonitrile solution that contains the cobalt(II) complex. For high quality crystals, recrystallization typically takes place over a 1 week period, or longer. The method can be applied to the preparation of other model coordination complexes and can be used in undergraduate teaching laboratories. Finally, it is believed that others may find this recrystallization method to obtain single crystals beneficial to their research.

Preparation of SNS CobaltII Pincer Model Complexes of Liver Alcohol Dehydrogenase

The preparation of SNS pincer cobalt(II) model complexes of liver alcohol dehydrogenase is presented here. The complexes can be prepared by reacting the ligand precursor with CoCl2&#183;6H2O and can then be recrystallized by allowing diethyl ether to slowly diffuse into an acetonitrile solution that contains the cobalt complex.

SNS 코발트(II) 간알코올탈수소효소의 집게 모델 복합체 의 제조

Chemical model complexes are prepared to represent the active site of an enzyme. In this protocol, a family of tridentate pincer ligand precursors (each ...

Dose Uptake of Platinum- and Ruthenium-based Compound Exposure in Zebrafish by Inductively Coupled Plasma Mass Spectrometry with Broader Applications

Metals and metal-based compounds comprise multifarious pharmaco-active and toxicological xenobiotics. From heavy metal toxicity to chemotherapeutics, the toxicokinetics of these compounds have both historical and modern-day relevance. Zebrafish have become an attractive model organism in elucidating pharmaco- and toxicokinetics in environmental exposure and clinical translation studies. Although zebrafish studies have the benefit of being higher-throughput than rodent models, there are several significant constraints to the model.
One such limitation is inherent in the waterborne dosing regimen. Water concentrations from these studies cannot be extrapolated to provide reliable internal dosages. Direct measurements of the metal-based compounds allow for a better correlation with compound-related molecular and biological responses. To overcome this limitation for metals and metal-based compounds, a technique was developed to digest zebrafish larval tissue after exposure and quantify metal concentrations within tissue samples by inductively coupled plasma mass spectrometry (ICPMS).
ICPMS methods were used to determine the metal concentrations of platinum (Pt) from cisplatin and ruthenium (Ru) from several novel Ru-based chemotherapeutics in zebrafish tissue. Additionally, this protocol distinguished concentrations of Pt that were sequestered in the chorion of the larval compared with the zebrafish tissue. These results indicate that this method can be applied to quantitate the metal dose present in larval tissues. Further, this method may be adjusted to identify specific metals or metal-based compounds in a broad range of exposure and dosing studies.

The increased rate of pharmaco- and toxicokinetic analyses of metals and metal-based compounds in zebrafish can be advantageous for environmental and clinical translation studies. The limitation of unknown waterborne exposure uptake was overcome by conducting trace metal analysis on digested zebrafish tissue using inductively coupled plasma mass spectrometry.

제브라피쉬에서 백금 및 루테늄 기반 화합물 노출의 선량 흡수는 유도적으로 결합된 플라즈마 질량 분광법과 광범위한 응용 분야에 의한 것입니다.

Metals and metal-based compounds comprise multifarious pharmaco-active and toxicological xenobiotics. From heavy metal toxicity to chemotherapeutics, the ...

Catalytic Reactions at Amine-Stabilized and Ligand-Free Platinum Nanoparticles Supported on Titania During Hydrogenation of Alkenes and Aldehydes

Ligands like amines are used in the colloidal synthesis approach to protect platinum nanoparticles (Pt NP&#39;s) from agglomeration. Normally, ligands like amines are removed by diverse pre-treatment procedures before use in heterogeneous catalysis as amines are considered as a catalyst poison. However, a possible beneficial influence of these surface modifiers on hydrogenation reactions, which is known from spectator species on metal surfaces, is often neglected.
Therefore, amine-stabilized Pt nanoparticles supported by titania (P25) were used without any pre-treatment in order to elucidate a possible influence of the ligand in liquid phase hydrogenation reactions. The catalytic activity of amine-stabilized Pt nanoparticles of two different sizes was investigated in a double-walled stirring tank reactor at 69 &#176;C to 130 &#176;C and 1 atm hydrogen pressure. The conversion of cyclohexene to cyclohexane was determined by gas chromatography (GC) and was compared to ligand-free Pt particles. All catalysts were checked before and after reaction by transmission electron spectroscopy (TEM) and X-ray photoelectron spectroscopy (XPS) for possible changes in size, shape, and ligand shell. The hydrogenation of cyclohexene in liquid phase revealed a higher conversion for amine-stabilized Pt nanoparticles on titania than the ligand-free particles. The hydrogenation of 5-methylfurfural (5-MF) was chosen for a further test reaction, since the hydrogenation of &#945;, &#946;-unsaturated aldehydes is more complex and exhibits various reaction paths. However, XPS and infrared spectroscopy (IR) proved that 5-MF acts as catalyst poison at the given reaction conditions.

This protocol shows a convenient method for comparing the catalytic properties of supported platinum catalysts, synthesized by deposition of nanosized colloids or by impregnation. The hydrogenation of cyclohexene serves as a model reaction to determine the catalytic activity of the catalysts.

알켄과 알데히드의 수소화 동안 티타니아에 지지된 아민 안정화 및 리간드가 없는 백금 나노입자에서의 촉매 반응

Ligands like amines are used in the colloidal synthesis approach to protect platinum nanoparticles (Pt NP&#39;s) from agglomeration. Normally, ligands ...

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3

Upatinib, a Janus kinase inhibitor drug, was developed by a biotech company to treat immune diseases. The compound tert-butyl (5-toluenesulfonyl-5h-pyrrole [2,3-b] pyrazine-2-yl) carbamate (ACT051-3) is an important intermediate of Upatinib. To date, the steady industrial production of this intermediate compound (ACT051-3) has not been reported. In this study, we described the specific synthesis method and process of the compound ACT051-3 in terms of laboratory synthesis, pilot scale-up, and industrial production. During the exploration of the process route for ACT051-3, many appropriate adjustments and improvements were made to the reaction conditions, finally leading to the successful development of the optimal industrial production process for ACT051-3. The reaction time was nearly doubled by changing the state of the potassium carbonate involved in the reaction, which greatly improved the reaction efficiency. Additionally, by introducing N,N-diisopropylethylamine (DIPEA) to the reaction, the amount of the expensive catalyst Pd(OAc)2 was reduced 2.5-fold, significantly lowering production costs, confirming the feasibility of this process route and the industrial production of ACT051-3, and satisfying market demand for this important intermediate.

Here, we present a protocol for the scaled-up synthesis of the intermediate tert-butyl (5-toluenesulfonyl-5h-pyrrole [2,3-b] pyrazine-2-yl) carbamate (ACT051-3) of Upatinib.

Upatinib 중간체의 확대 준비, ACT051-3

Upatinib, a Janus kinase inhibitor drug, was developed by a biotech company to treat immune diseases. The compound tert-butyl ...

A Tripeptide-Stabilized Nanoemulsion of Oleic Acid

We describe a method to produce a nanoemulsion composed of an oleic acids-Pt(II) core and a lysine-tyrosine-phenylalanine (KYF) coating (KYF-Pt-NE). The KYF-Pt-NE encapsulates Pt(II) at 10 wt. %, has a diameter of 107 &#177; 27 nm and a negative surface charge. The KYF-Pt-NE is stable in water and in serum, and is biologically active. The conjugation of a fluorophore to KYF allows the synthesis of a fluorescent nanoemulsion that is suitable for biological imaging. The synthesis of the nanoemulsion is performed in an aqueous environment, and the KYF-Pt-NE forms via self-assembly of a short KYF peptide and an oleic acids-platinum(II) conjugate. The self-assembly process depends on the temperature of the solution, the molar ratio of the substrates, and the flow rate of the substrate addition. Crucial steps include maintaining the optimal stirring rate during the synthesis, permitting sufficient time for self-assembly, and pre-concentrating the nanoemulsion gradually in a centrifugal concentrator.

This protocol describes an efficient method to synthesize a nanoemulsion of an oleic acids-platinum(II) conjugate stabilized with a lysine-tyrosine-phenylalanine (KYF) tripeptide. The nanoemulsion forms under mild synthetic conditions via self-assembly of the KYF and the conjugate.

올레산의 Tripeptide 안정 Nanoemulsion

We describe a method to produce a nanoemulsion composed of an oleic acids-Pt(II) core and a lysine-tyrosine-phenylalanine (KYF) coating (KYF-Pt-NE). The ...

생체공학

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay

Spirocyclic heterocycles have recently been reported in literature to be potential drugs for cancer therapy. The synthesis of these novel orthogonal ring systems is challenging. An efficient methodology to synthesize these compounds was recently published that described the solid phase synthesis in four steps rather than the previously reported five steps. The advantage of this shorter synthesis is the elimination of the use of toxic reagents. Low-loading Regenerating Michael (REM) linker-based resin was found to be crucial in the synthesis as high-loading versions prevented the addition of reagents containing bulky phenyl and aromatic side chains. The colorimetric 3-(4&#8242;,5&#8242;-dimethylthiazol-2&#8242;-yl)-2,5- diphenyltetrazolium bromide (MTT) assay was used to examine the cytotoxicity of micromolar concentrations of these novel spirocyclic molecules in vitro. MTT is readily available commercially and produces relatively fast, reliable results, making this assay ideal for these spirocyclic heterocycles. Orthogonal ring structures as well as furfurylamine (a precursor in the synthesis method containing a similar 5-member ring motif) were tested.

Here, we describe a bioassay using 3-(4&#8242;,5&#8242;-dimethylthiazol-2&#8242;-yl)-2,5- diphenyltetrazolium bromide (MTT) to test previously synthesized spirocyclic oximes.

기능화된 스피로사이클릭 헤테로사이클 합성 및 세포독성 분석

Spirocyclic heterocycles have recently been reported in literature to be potential drugs for cancer therapy. The synthesis of these novel orthogonal ring ...

이핵 항암제로 플래티넘 비스 피리딘 계 리간드와 이들 착물의 합성 아미드 커플 링 반응

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