D1 Purchase Description.doc

PURCHASE DESCRIPTION

1. Statement of Need and Purpose:

The Medicinal Chemistry Section (MCS) focuses on the design, synthesis and pharmacological evaluation of: (1) typical dopamine uptake inhibitors that bind with high affinity and selectivity to the dopamine transporter but are not cocaine-like in animal models of psychostimulant abuse; (2) dopamine D3 receptor antagonists and partial agonists as in vivo tools for the elucidation of the role these receptors play in addiction and impulsive behaviors; (3) novel D2 and D3 receptor biased agonists; and (4) fluorescent ligands to study structure and function of the dopamine and serotonin transporters. MCS needs a Fourier Transform Nuclear Magnetic Resonance (FT NMR) spectrometer to analyze the molecular structure of all compounds synthesized in the lab. The FT NMR is the only accepted analytical method in organic and medicinal chemistry to determine and assign compounds’ structures, relative and absolute stereochemistry, purity and possibly conformational changes in either sample solutions or solid state. NMR spectroscopic data are absolutely necessary in order to publish chemistry manuscripts or patents, since NMR spectra are mandatory and required by any publisher. The NMR spectra provide key analytical data that is essential for chemical structure determination and provides required reproducibility when repeating synthetic strategies.

2. Background Information and Objective:

Background Information The Medicinal Chemistry Section’s (MCS) current NMR instrument is more than 20 years old. This is beyond a normal “life” for a high-magnetic field instrument. In the past year we have had to arrange frequent service to our NMR as it has not been running properly and required a professional engineer to fix it. This has caused significant down time for the lab for which the NMR is used every day by all of the chemists. In December 2021, our magnet underwent what is commonly called a “quench”, meaning that our instrument lost the ability to create the magnetic fields required for chemical strucutral anlysis. This is a very serious and can be dangerous event, but also a common problem with older super-conducting magnets. We, despite having a maintenance agreement, couldn’t get engineers in to recharge the magnet until mid-February, which was a serious problem for the lab. Further, it costs the lab ~$6000 in liquid helium to keep the magnet cool after the quench and then recharge it. Our current NMR was made by Varian, a company that was later taken over by Agilent. Although Agilent continues to hold the maintenance agreement, they have limited engineers, which causes us to have to wait for days, weeks or even months for a repair. In addition Agilent no longer sells NMRs. So, although they have been able to temporarily restore the instrument functionality, there is no guarantee that another quench won’t happen in a short time. Hence for our continuing daily research reqirements we need to replace it with a new 400 MHz NMR.

Importance of the Requirement

As stated above the NMR is the most essential instrument in a chemistry lab. It is absolutely essential for our work. Without it, or with an old instrument that is not reliably functioning, the lab is unable to proceed with the synthesis and characterization of our novel molecules which is essential to continue our research. Moreover, many intramural and extramural collaborators rely on our chemistry lab to provide compounds for many research projects, spanning from in vitro pharmacology to in vivo pre-clinical and clinical studies. With our work slowing down, unfortunately these other labs collaborating with us will suffer a delay in time-sensititve projects.

3. Generic Name of Product: Fourier Transform Nuclear Magnetic Resonance (FT NMR) spectrometer.

4. Purchase Description:

The ECZ Luminous (JNM-ECZL series) is a Fourier Transform Nuclear Magnetic Resonance (FT NMR) spectrometer equipped with state-of-the-art digital and high frequency technology. The highly integrated Smart Transceiver System, a high-speed, high-precision digital high-frequency control circuit, enables further miniaturization and high reliability of the spectrometer. It is capable of high-field and solid-state NMR measurements while maintaining the size of a conventional low-field solution NMR system. The new Multi Frequency Drive System enables multi-resonance measurements in a standard configuration, providing a wider range of solutions.

5. Salient characteristics FT NMR Spectrometer Specifications

400 MHz, 9.4 T NMR Spectrometer

Frequency: 400 MHz Sample Type: Solution

Number of channels: Minimum 2

Power amplifier for high frequency: Minimum 50 W

Power amplifier for low frequncy: Minimum 150 W

Magnetic field gradient amplifier: Minimum 10 A Console size (W×D×H): Approximately 536×730×855 mm

400 MHz, 9.4 T NMR Spectrometer

Basic Broadband Pulsed Field Gradient NMR System Includes:

NMR Pulse Programmer

Includes pulse programming language with support for minimum eight-dimensional data collection;

Includes automatic high-speed pulse sequence decomposition to identify and exploit parallelism within a pulse sequence;

Includes master timing sequencer unit with minimum 5 ns timing resolution;

Includes mMinimum event time 20 ns depending on event;

Includes minimum 2 GB pulse sequence / waveform memory for shaped rf control.

Spectrometer RF Generation System

Includes modular RF backplane with sequencer bus controlling minimum 8 frequency sources

Includes two full-band transmitter modules covering 5 to 1,300 MHz with up to 159 dB attenuation, the final output frequencies must be filtered appropriately to match the NMR spectrometer operational frequencies.

Includes direct digital synthesis (DDS) units of the intermediate frequency (IF) with:

0.001 Hz offset frequency resolution

0° to 360° phase shift with 0.005° phase resolution

0 to 100% RF shape amplitude with 0.01% resolution

0 dB to 79 dB Step Attenuator with 1 dB step

User-defined pulse shapes (phase, frequency, amplitude) including predefined pulse shapes (sinc, gauss, seduce, eburp, iburp, uburp, shifted laminar)

User-defined decoupler modulations including pre-defined modulations (Waltz, Waugh, Garp, MPF, Wurst)

Includes homonuclear and heteronuclear decoupling modes.

NMR RF Power and Field Gradient Amplifiers

Includes linear, class AB 50-watt RF power amplifier for high-band (365 to 430MHz)

Includes linear, class AB 150-watt RF power amplifier for low-band (10 to 170 MHz)

Includes Z-axis pulsed field gradient amplifier delivering 10-ampere current.

Magnet Console and Preamplifiers

Includes low noise GaAs high sensitivity preamplifier for high-band and low noise wideband Includes SiGe preamplifier low-band frequencies

Includes active transmit/receive duplexer

Includes liquid cryogenic level monitoring system for helium and nitrogen

Includes relay switching for automatic 2H gradient shimming.

Digital Receiver

Includes wide-band high sensitivity Digital Quadrature Detection receiver with minimum 16 bit 100 MHz ADC digital IF with minimum 64 bit signal averaging and phase and frequency offset control providing sweep widths from 50 Hz to 10 MHz.

Lock and Shim System

Includes deuterium internal digital lock system with computer-controlled auto-lock functions

Includes gradient shimming capability using shim set Z1 gradient or PFG Z gradient

Includes room temperature matrix shim system (25 shims) and power supply

Includes mMatrix shim design minimizes orthogonal shim interactions.

AIR/VT System

Includes computer controlled air controller for sample loading and spinning

Includes variable temperature controller, range -170° C to +250° C in 0.1° C steps. (The operational VT range varies with the probe.)

The NMR system must include a heater for operation above ambient temperature, and the option to separately purchase a LN2 Dewar kit for operation below ambient temperature Spectrometer power supply, chassis, and table

Includes single phase 100 to 240 V AC, 50/60 Hz, 15A

Includes worktable for computer and printer

NMR Magnet, 9.4T, Shielded, 54mm, Year Hold

Includes shielded superconducting magnet solenoid, cryostat and cryo-shims with room temperature bore diameter of minimum 54 mm operating at minimum 9.39T providing NMR observation of 1H at 400MHz.

Performance Specifications:

Field Drift: <= 4 Hz/hr

Radial 5 Gauss Line: 0.5 m (19.7 in)

Minimum Ceiling Height: >= 2.84 m (112 in)

Helium Hold Time: >=365 days

Nitrogen Hold Time: >=14 days

Includes: Liquid cryogenic level sensors for helium and nitrogen, liquid nitrogen braided stainless steel fill hose, and liquid helium transfer tube.

Vibration Damping Table, Pneumatic

Pneumatic Anti-Vibration Table for 400 MHz Magnet

Effective for:

Vertical Vibration greater than 2 Hz

Horizontal Vibration greater than 2.2 Hz

Note Resonance Conditions:

Vertical 1.3 Hz

Horizontal 1.5 Hz Digital Auto Tune Probe Includes minimum 5 mm high sensitivity ROYAL HFX NMR probe

Provides ¹H{¹⁹F}, ¹⁹F{¹H}, ¹³C{¹H,¹⁹F}, and X{¹H,¹⁹F} experiments with switchable magnet idler coil tuning and no performance loss in standard 1H or ¹⁹F mode.

Includes coils optimized for proton, fluorine, and multinuclear observation and decoupling

Includes digital auto-tune and match ready, Z-axis pulsed field gradient coil, 2H lock

Nuclei include: 1H, ¹⁹F, ³¹P to ¹⁵N, ³⁹K, and ¹⁰⁹Ag Includes variable Temperature operation from -100° C to +150°C Spinner Housing Retention time of liquid helium allows for reduced frequency of helium refill to at least once every year Includes a relatively smaller stray magnetic field from the inside of the magnet to the outside Compact size same as regular 400 MHz magnet

Freer layout of installation room Auto Tuning Unit Provides for automatic tuning and matching of compatible NMR probes with optimal sensitivity and pulse widths.

10L N2 Dewar

For low temperature NMR operation (Ambient to -150° C)

Actual temperature range may be limited by the NMR probe.

Includes: Non-Magnetic 10 liter liquid nitrogen Dewar, Dewar Adapter with heater and LN2 Dewar filling tool.

Auto Sample Changer

Includes minimum 24-position Auto-Sample changer for NMR systems

Includes minimum 24 each 5mm variable temperature compatible sample spinners

Must mount on top of magnet bore IT Specifications:

PC Workstation Complete spectrometer control and data processing through a personal computer that equals or exceeds the following specifications: Microsoft Windows 10 Pro 64-bit operating system; 3.0 GHz (4.4 GHz Turbo) 6 Core CPU, 16 Gbyte RAM, 2 Tbyte disk drive, 2 Gbyte color graphics card, 24" color flat screen display, DVD+/-RW drive, alphanumeric keyboard, mouse, and

Software

Includes comprehensive FT-NMR Software including 1, 2, 3-D data acquisition, processing, display, and plotting for Microsoft Windows™ or

Apple macOS™ operating systems

Includes customer site-wide license for NMR software

Includes automated 'point and click' NMR operation software with automatic gradient shimming, user-defined automation and data presentation

Includes macro programming language

Includes diffusion order NMR spectroscopy (DOSY) data analysis and presentation.

6. Quantity:

7. Warranty: The complete system will have a 12-month warranty. Under this warranty policy the labor necessary to repair the instrument and all parts (except consumables) are provided by vendor at no cost to the customer. All service performed on this equipment shall be provided by certified and factory trained technicians. Contractor shall provide any required replacement components due to malfunctions on-site and will include all travel, parts and labor.

8. Delivery Date:

Freight Terms: FCA: DESTINATION, INSIDE DELIVERY

The contractor shall deliver and install the required equipment within seven (7) months after receipt of order. On-site training must take place at the customer site within two (2) weeks of equipment installation. Shipping and installation included with quotation (cryogens are the responsibility of the customer). Performance will be monitored by Medicinal Chemistry Section staff. Instrument delivery and installation will be provided by qualified personnel to ensure that the instrument is properly installed and ready to use. This includes the physical setup, set of NMR reference standards for NMR tests, calibration and performance verification of the system. Initial customer training performed by installation personnel. On-site training with an NMR pplications chemist after instrument acceptance.

Delivery Address:

NIH BRC, Suite 200

251 Bayview Blvd., Rm. 04A521

Baltimore, MD 21224

9. Period of Performance: Base year includes one-year warranty

10. Option(s): 4 options years for service coverage