About

Abby and Howard P. Milstein Chemistry Core Facility

The Chemistry Core is moving to MSKCC and will not be available for scheduling. Please contact Todd Evans with any questions or concerns. To reach the MSKCC Chemistry Core contact Ouathek Ouerfelli (Ouerfello@mskcc.org).

 

Mission Statement

Our mission is to provide the equipment and expertise required to perform any type of chemical task necessary to assist in the successful completion of a collaborator’s project. This includes all forms of chemical synthesis (API, intermediate, probe, etc.), compound identification and purification, and analytical chemistry.

Overview of Services

The Abby and Howard P. Milstein Chemistry Core Facility (MCCF) was established in 2006 through the generosity of Weill Cornell Overseer Howard P. Milstein. The facility is located on the 16th floor of the Belfer Research Building and has helped investigators from nearly every department within Weill Cornell Medicine, both clinical and basic science. Though primarily designed to assist with synthetic chemistry, our expertise and equipment allow us to provide essential analytical services as well. Major equipment includes UPLC/MS, with mass detection up to 3000 amu, preparative HPLC/MS, preparative HPLC, GC/MS, IR, automated microwave synthesizer, and automated chromatography instrumentation. The recent acquisition of an Agilent RapidFire LC/MS system dramatically expands our analytical capabilities. For example, we are now able to offer fragmentation analysis of analytes using the triple quadrupole mass spectrometer.

 

Our work is accomplished through the design and execution of efficient and economical synthesis of chemicals that are either not readily available through commercial vendors or are prohibitively expensive. Such compounds may be known in the literature, or entirely novel, and can be generated in virtually any quantity desired, from sub-milligram quantities to tens of grams, using equipment currently within the lab. Each molecule generated is fully characterized by modern analytical techniques.

 

Synthetic projects generally fall within two subcategories:

  • synthesis of a single compound that is known in the literature, or obtained from a chemical screen
  • synthesis of compounds with unknown utility, but are predicted to have desirable properties

Analytical projects also generally fall within three subcategories:

  • identification of unknown and known molecular entities
  • evaluation of extracts from cellular assays
  • analysis of biological extracts, serum, or plasma

The Milstein Chemistry Core Facility is supported by the Howard and Abby Milstein Foundation through its medical philanthropy. To learn more about this charity, please visit the Howard and Abby Milstein Foundation website.

Facilities

The Core Facility is located on the 16th floor of the Belfer Research Building and is supported by state-of-the-art resources. Standard benches are available for each scientist and include rotary evaporators with both low and high vacuum capacity, a fume hood with argon manifolds, an ISCO automated chromatography system, and a Radleys StarFishTM multi-experiment workstation. In addition, the facility is equipped with a full array of chromatography and analytical equipment, including the following: Büchi Sepacore binary gradient low/high pressure automated chromatography system; Acquity SQD UPLC with simultaneous PDA, fluorescence, and mass detection (up to 2000 amu); Acquity H-Class UPLC with simultaneous PDA, fluorescence, and mass detection (up to 1250 amu); Acquity I-Class UPLC with simultaneous PDA, and mass detection (up to 3000 amu); Preparative HPLC with PDA detector; Auto-Pure Preparative HPLC with simultaneous PDA, ELSD, and mass detection (up to 3000 amu); GCMS with autosampler, capable of internal, external and hybrid ionization; and TENSOR 27 series FT-IR spectrometer equipped with a Diamond ATR for fast and easy IR sampling. The Core has acquired an Agilent RapidFire LCMS system and now offers it as a service. This system matches the latest Agilent UPLC (1290 Infinity II) and RapidFire high-throughput SPE systems with an Agilent 6495 triple quadrupole mass spectrometer (QQQ). The combined utility of these systems provides unparalleled sensitivity and speed for chemical analysis. The UPLC/MS portion of the instrument complements prior instrumentation in the lab by adding the ability to obtain fragmentation data, and effectively drops the lower limit of quantitation (LLOQ) at least an order of magnitude, while the RapidFire adds the ability to run high-throughput mass analysis suitable for enzymatic assays, drug binding, and stability studies, and metabolomics, to name a few.

Services

The Core provides the following services:

  • Consultation on experimental design and procedures, the commercial availability of individual chemical compounds and/or reagents, and the feasibility of chemical structures
  • Chemical synthesis of compounds that are not readily available, or are prohibitively expensive from external vendors
  • Synthesis of assay development tools and reagents including fluorescently labeled compounds; affinity labeled compounds; cross linker-tethered molecules; labeled (13C, 2H, 15N) and radiolabeled (3H, 14C, 32P, 125I, etc.) compounds for preclinical and clinical pharmacological studies, which cannot be directly addressed by the Citigroup Biomedical Imaging Center
  • Synthesis of compounds in quantities that allow for in vitro and in vivo assays, and follow-up assays when warranted
  • Large-scale chemical synthesis of compounds with demonstrated biological activity in primary assays, to provide material for further investigation
  • Confirmatory synthesis of compounds identified via high-throughput screening
  • Structure-activity relationship (SAR) studies on validated pharmacophores to optimize targeting, specificity, and bioavailability while minimizing toxicity
  • Structure determination of unknown molecular entities
  • Detailed chemical analysis of reaction mixtures, cell extracts, and bioassays
  • Molecular modeling and in silico screening using a variety of computational tools, including the Schrödinger software suite 

Plan of Operation

Submission of Synthetic Requests

 

Investigators can submit their request(s) either directly to the MCCF Director or through the iLab website using a custom form. Requests should include background information, including any known literature precedent, and a brief statement concerning the nature of the project. Once the request has been fully examined to determine feasibility, estimated cost, and a projected time to completion, an initial consultation will be arranged. During this consultation, the Facility Director will discuss the request regarding its complexity and synthetic route, suggesting alternative routes when applicable. This will also establish the time frame for synthetic milestones, when warranted, and expected time to delivery.

 

The scheduling of each request takes the following into consideration:

  • length of the synthetic sequence (i.e. overall number of steps)
  • literature precedent
  • scale of synthesis and estimated complexity
  • investigational priority within the Core (i.e. total number of current projects)

Synthesis

 

Once project parameters are accepted, synthetic efforts begin. Due to the extensive synthetic expertise within the MCCF, original synthetic methods may be adapted and developed so that the project can be completed in an efficient, timely, and cost-effective manner. All intermediates are fully characterized using the latest analytical techniques, and experimental details are kept offsite in an electronic laboratory notebook (ELN, Scilligence). Each chemist has their own ELN, and projects are further divided within the ELN by PI and project.

 

Delivery

 

Upon project completion, or as milestones are reached, the product(s) are delivered directly to either the end user or PI, depending on preference. Each compound is supplied with a unique compound code that is directly traceable to its synthesis, should issues arise or resynthesis becomes necessary. In addition, the complete spectral identity (NMR, LC/MS, etc.) of each compound will be provided if so desired.

 

Development

 

When appropriate, another consultation could be scheduled to discuss biological test results. This would allow for an assessment of the project and to decide the optimal course of action. If further synthetic work is deemed necessary, this process could be reiterated.

 

Submission of Analytical Requests

 

Investigators can submit their request(s) either directly to the MCCF Director or through the iLab website using a custom form. Requests should include background information, including any known literature precedent, and a brief statement concerning the nature of the project (when applicable). Once the request has been fully examined to determine feasibility, estimated cost, and a projected time to completion, an initial consultation will be arranged. During this consultation, the Facility Director will discuss the request in terms of its complexity and requirements for data analysis. This will also establish the time frame for analytical milestones, when warranted, and expected time to completion.

 

The scheduling of each request takes the following into consideration:

  • complexity of analysis (ex. is method development required?)
  • literature precedent
  • number of samples to be analyzed, including post collection data analysis
  • investigational priority within the Core (i.e. total number of current projects)

     

Data Collection

 

Once project parameters are accepted, data collection begins. If method development is required, standards are obtained so that the method can be fully validated before running experimental samples. Depending on the nature of the project, data collection occurs either with varying degrees of precision. For example, the analysis of a sample to confirm identity and purity is not run to the same level of precision as a sample being analyzed for QA/QC studies, or samples being analyzed for use in a clinical trial. Although all samples are run with precision and accuracy in mind, our expertise and instrumentation allow for special care to be used, when warranted. This level of detail is laid out and confirmed at the outset of each project.

 

Data Analysis

 

Data analysis can be as simple as returning a chromatogram indicating the retention time and mass information to a user, or obtaining integration data for a series of chromatographic events and returning the raw information to the user for them to interpret. We can also provide a full analytical workup if desired.

 

 

Location and hours of operation

Hours Location

 

Monday-Friday, 9am-6pm,       
or by appointment

 

 

413 E 69th Street
16th Floor, Room BB-1656
New York, NY
10021
 

 

Links and Resources

  1. http://corefacilities.weill.cornell.edu/syn_core.html

Contacts

Name Role Phone Email Location
J David Warren, PhD
Core Director
 
(646) 962-6138
 
jdwarren@med.cornell.edu
 
BB-1612
 

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