Introduction to Quartus II Software Design using QSim for Simulation

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In this tutorial, we will show you how you capture the schematic design for the automatic door opener circuitusing Altera Quartus II software.

The Problem

We are designing a circuit for an automatic door like those you see at supermarkets. The door should open only when a person is detected walking through or when a person presses a switch (such as the wheelchair button) to have the door open. The door should only operate if it has been unlocked.

Altera is configured; An interesting note: Altera under its University Program is providing FPGA’s at subsidised rate Check this link for more details Altera University Program I am planning to get one of my own very soon 😀. Please Comment for improvement of future posts – Nishant Nath. Download Quartus Prime software, and any other software products you want to install, into a temporary directory. Download device support files into the same directory as the Quartus Prime software installation file. Change the file permission for all the setup (.run) files by running the command: chmod +x.run.

• output: f = 1 (Opens Door)
• inputs
  • p = 1 Person Detected
  • h = 1 Switch Holding the Door Open
  • c = 1 Door Closed/Locked
• Want door to open when
  • the door is unlocked and person walking through (c=0 and p=1)
  • the door is unlocked and the switch is set to hold it open (c=0 and h=1)

E: Drive or flash drive

While working in the lab, you will want to work from either the E: drive on the lab machines or for a flash drive.You can copy your directory to your I: drive at the end when you are done, but there are problems working directly on the I: drive in Quartus II. Be sure to copy your files to the I: driveor a flash driveafter you are done,since files on the E: drive will be erased.
Each time you create a new project in Quartus II, create a new project directory so that all of the files for each project are in one place and not mixed up with files from other projects.

Getting Started with Altera Quartus

Launch the Altera Quartus software. You should see a screen such as this:

Creating a New project

Select the File → New Project Wizard; a window like the following will appear.

To select the working directory use the button to browse and select E:CP120intro.
Name the project DoorOpener. (Note that the next field gets filled in automatically.)Select Finish.
Don't uses spaces in file or directory names.

Creating a new Schematic design

Select File → New - A window as seen in the following picture will open.

Select 'Block Diagram/Schematic File' and press OK.

This should open a pane where you will design your circuit. This pane is designated Block1.bdf. Save this graphic design file as DoorOpener in your 'intro' directory. The file will be given the bdf extension; bdf stands for block design file and contains schematics, symbols or block diagrams.

Adding text

1. Select the A below the arrow to the left of your Block Diagram/Schematic File window (also known as the palette).
2. Select a point near the top left in the window with the left mouse key.
3. Type your name and then hit the Enter key.
4. Type your project name and then hit the Enter key.
5. Type the following equation, f = hc' + pc' , and then hit the Enter key.
6. Hit the Esc (escape) key to end text additions.

Adding a Component

1. Click the library icon.The Symbol dialog box will appear. This window lists the available Altera libraries as seenin this image.
2. Expand the /altera/quartus12.1/quartus/libraries folder, expand the primitives folder and then expand the logic folder.
3. In the logic folder, select the and2 component by double clicking on it (or by selecting it with a single click, then selecting OK).
4. Click the pointer at the desired location in the Block Diagram/Schematic Editor window to insert the AND symbol into the design file.

Repeat these steps to enter an OR (or2) gate and a NOT (not) gate.

(If you wanted to add multiple NOT gates, you could select the Repeat-insert mode box.)

In the same manner that you placed a gate onto the palette, add three input pins and one output pin from the Symbol libraries. Input pins can be found under primitives | pin | inputs. Output pins can be found under primitives | pin | outputs.

Name your input and output pins as you name them in your equation. Double click on the pin name to change its name.
Never use spaces in pin names; e.g. 'input 1' is a problem - 'input1' and 'input_1' are ok.

Rearrange your devices in approximately the placement you would like for the logic diagram you are trying to construct. You can move a component by selecting it with your mouse, holding down the left button and moving it to another location on the palette.

Save your design. It is a good idea to save your design often, just in case something bad happens .Save the bdf file with the same name as the project.
Don't use spaces in any file names.

Wiring your circuit

Select the orthogonal node tool. Place your pointer on the output of one of the input pins and hold the left mouse button down. You should see a cross-hairs or + appear at the output.

Drag your pointer to the input of the AND gate. Every time you release the mouse key, the line (wire) ends. If your wire did not reach the AND gate, you can add to the wire by putting your mouse over an end of the wire and again selecting it with your left mouse button and dragging your mouse to another position.
Don't run wires along the edge of a device. This can cause simulation problems.
Don't leave inputs and outputs right next to the chips. Make sure you can actually see some wire between them, otherwise you may have simulation problems.

Note: Make sure you do not make the wire too long. If you drag it too far you will see an x; and this is considered an open connection and your design will not compile.

To delete a wire or a portion of a wire, simply click on it (it should change color to indicate selection) and press the delete key.

If wires are connected to the component as you are moving it, the wires will drag and stay connected to the component. This is referred to as 'rubber banding' and is a feature of all major schematic entry design packages. (You can turn rubberbanding on and off using the rubberbanding tool. )Add the rest of the wires needed to connect the logic diagram.

The window should look something like image below. Save your design.

Printing

We will not print today. But you will need to know how for your project.

To print, go to File | Print. If you want to change what appears on the printout or how it appears, go to File | Page Setup change print settings. Before printing, you can view what the print will look like by selecting File | Print Preview

Choosing a Device

The programmable device which we'll use for our design can be chosen now.

Select Assignments | Device from the pull-down menu.

Select MAX7000S from the 'Family' pull-down list.Select the 'Specific device selected' and then choose EPM7064SLC44-10, which is the device we are using in our lab. Select 'OK.'

If you get a message like this, don't worry; it's fine.

Circuit Compilation

You will need to compile your design to ensure you do not have any errors in your circuit (e.g. you do not have any open connections, etc.)

Click on Processing | Start Compilation to start compilation.

If you get any error messages, you'll need to fix your circuit before you can simulate it.

Common causes of errors

Download Altera University Program Qsim Free Version

If you have one of these issues, you need to fix it.

• Do you have a project (qpf) open, or just a drawing (bdf)?
• Is your project on the I: drive?
• Are your project (qpf) and drawing (bdf) files in differentdirectories?
• Are there any spaces in your directory or file names?

Circuit Simulation

1. 
   To open QSim, File | New | New University Waveform File.
2. Select Edit | Insert | Insert Node or Bus.
3. Select Node Finder.
4. Select List.
5. Select the double right arrow to choose all.
   
6. Select OK.
7. Select OK.
8. If you have multiple inputs, you can select a bunch and group them with one counter.
9. Select your input(s), and pick Overwrite Count Value. Select OK.
   
10. Select File | Save As to give this file a name in your project directory. It will have a VWF extension for Vector Waveform File.
11. In the Main window, select Simulation | Options and then select Quartus II Simulator. Select OK.

    Note: If you haven't chosen a Cyclone device, the Quartus II Simulator option will be greyed out. In that case, assign the device to any Cyclone II device and recompile.

12. In the Main window, select Simulation and then select Run Functional Simulation.
    ( Alternatively, you can you the button on the tool bar.)
13. Now you should see your simulation output with the outputs defined. Note: The file will indicate 'read-only' meaning you can't edit it.
    You can expand the grouping:
14. You can navigate around the timeline, zoom in and out, etc.
    

    This part of the output shows that when the inputs are all zero, the output is also zero.

    
    

    This part of the output shows that when c and h are low, and p is high, the output is high.

    
    

    This part of the output shows that when c and p are low, and h is high, the output is also high.

    You can repeat this process to check all of the eight possible input combinations.

    
    
15. Now if you want, you can go back to the simulation settings and choose Timing instead of Functional to see the effects of propagation delay. In the Main window, select Simulation and then select Run Timing Simulation.
    ( Alternatively, you can you the button on the tool bar.)

Copy your directory from the E: drive to the I:drive or a flash drive. You'll use this project for future labs.

Demonstrate the circuit to the lab demonstrator.

Delete everything from the E: drive so your files don't get used by someone else later.

• Altera Corporation - University Program April 2014 1. QUARTUS II INTRODUCTION USING VERILOG DESIGNS For Quartus II 13.1 2Background Computer Aided Design (CAD) software makes it easy to implement a desired logic circuit by using a programmable logic device, such as a field-programmable gate array (FPGA) chip. A typical FPGA CAD flow is.
• Page 1 University Program’s web site. An easy way to begin working with the DE1-SoC Computer and the Nios II processor is to make use of a utility called the Altera Monitor Program.

Quartus II Tutorial IntroductionAltera Quartus II is available forWindows and Linux. The instructions here are from version 11.0, withsome updates for versions 12.0, 12.1 and 13.0.

This is accomplished by selecting “File - New - University Program VWF”. Test vectors created with this tool can be used in simulation of your circuits by running the ModelSim-Altera simulation tool. The simulator can be started from within the Waveform Editor, or by using the Altera Nativelink flow.

I try to keep it up todate.On my YouTube channnel, I have a.Using Quartus II. Simulation Note: Since version 11.1 of Quartus II, the QSimsimulator has been automatically included with Quartus II, forWindows and Linux. For simple simulations, it is easy to use.Following are instructions for simulations using either one.(using QSim) (using ModelSim).In this tutorial, we will showyou how you capture the schematic design for the automatic door opener circuitusing Altera Quartus II software.The ProblemWe are designing a circuit for anautomatic door like those you see at supermarkets.

The door shouldopen only when a person is detected walking through or when aperson presses a switch (such as the wheelchair button) to havethe door open. If you're using a version of Quartus II lower than13.0, use the.Simulation using QSim for version 13.0 Note: In version 13.0 of Quartus II, QSim can beopeneddirectly from within QuartusII, however it only works with Cyclone devices.

If you'vealready chosen a non-Cyclone device, switch to a Cyclone device to dothesimulation. Simulation using QSim for versions 11 and 12 Note: QSim can't be opened automatically from within QuartusII. You can invoke it by typingquartussh -qsimat a command prompt. (Run this in the directory where you find theQuartus II executable file.).

Open the Altera U.P.

Full text of 'UNIVERSITY OFIILINOIS LIBRARYAT U ^.NA-CHAMPAIGNDigitized by the Internet Archivein 2012 with funding fromUniversity of Illinois Urbana-ChampaignTOPICSI Semester 1979-80X-— ^Generation and Synthetic Utilityof Carbanions Stabilized byDivalent SulfurPeter BeckerrThe Design, Synthesis, and Biology ofIntercalating AgentsDavid W. RobertsonJ HERTZBERG - NEW METHOD, INC. EAST VANDALIA ROAD, JACKSONVILLE, ILL. 62650Q, -TITUE NO.B.ACCOUNT NO.:NRTK«LOT AND TICKET NO.132257982.PT ♦ 1Q.

547.IG»L 5^- R' I2 T. C=SCH 2 LiLl y +1 R = Ph Y32 R = Me - AReaction of a-lithiosulfides with a variety of electrophiles givesthe expected products in good yield; j2.j. 2^ with carbon dioxide gives2-methylthioacetic acid. Methylenation of ketones 10 has been performedwith 1 and 1 along with higher homologs has been used in the synthesis ofepoxides. 11 Homologation of trialkyl boranes 12 has been effected with 2^,as well as the synthesis of terminal alkynes from carboxylic acids.

13Trost has formed cyclobutanones 14 and cyclopentenes 15 from adducts ofphenylthiocyclopropyl lithium with ketones.Allyl and benzyl sulfides are more readily metallated, and even thedianions of allyl and benzyl thiol 16 have been reported. Trialkyl boranecomplexes 17 and complexation with heteroatoms 18 have been used to directa-alkylation of ambident allyl anion J3. However, the copper reagent givespredominantly y- alky la t ion. 19 Reported syntheses of terpenes, 20 jasmonoids 21and prostaglandin F 2 22 employed species J3. Cecropia juvenile hormoneshave been made via dihydrothiapyrans.

23 Alkylation followed by sigmatropicrearrangement has proven useful. 24Metallated vinyl sulfides serve as acyl anion equivalents and havebeen prepared by addition of organometallic reagents to acetylenic sulfidesand thioketenes and transmetallation.

25 Direct proton abstraction is theormost widely used route and there have been a number of recent examples. DMetallation of 1,3-dien-l-yl sulfides has also been reported. 27 Higherhomologs have been metallated in the a-position.

28Derivatives of thiols such as thioimidates, dithiocarbonates and thio-esters have been deprotonated on the sulfur-bearing carbon and are thoughtto be dipole stabilized 4. 29 Mono and dithiocarbamates also have beendeprotonated.

30 The above compounds are generally limited to the methyland allyl cases; however, a-lithioisopropyl 2,4,6-triisopropylthio-benzoate has been formed in good yield. Gillman and F. Soc, 71, 4062 (1949).2. Chen., 31, 4097 (1966)3. Peterson, ibid., 32, 1717 (1967).4. Bryson, Tetrahedron Lett., 1961 (1977).5.

Mendoza and D. Chem., 44, 1352 (1979).6. Screttas and M. Micha-Screttas, ibid., 44, 713 (1979); T.

Daniewski and R. Weisenfeld, Tetrahedron Lett., 4665 (1978).7. Damonc, and A. Krief, ibid., 1617 (1975);D. Meyer, and A. Chem., 846 (1977).8.

Peterson, Organomet. Rev., A 2, 295 (1972).9. Pichat and J. Beaucourt, J. Com., 10, 103 (1974).10.

Kurata, Tetrahedron Lett., 737 (1972);T. Shono, et al., ibid., 2807 (1978); R. Sowerby and R. Soc, 94, 4758 (1972).11. Shanklin, et al., J.

Soc, 95, 3429 (1973); W. H.Pirkle and P. Chem., 43, 3803 (1978); W.

Altera University Program Qsime Online

H.Pirkle and P. Rinaldi, ibid., 44, 1025 (1979).12. Nigishi, et al., J. Chem., 40, 814 (1975). Yokomatsu, and S.

Shibuya, ibid., 43, 4366 (1978).14. Trost, et al., J. Soc, 99, 3080,3088 (1977); B. M.Trost and J.

Chem., 43, 2938 (1978); B. Vladchick, Synthesis, 821 (1978).15. Soc, 98, 248 (1976).16.

Seebach and K.-H. Geiss, Angew.

Chem., 86^, 202 (1974); M.Pohmakotr, K.-H. Geiss, and D.

Seebach, Chem. Ber., 112, 1420 (1979).17. Yatagai, and K. Soc, Chem.Commun., 157 (1979).18. Hayashi, and T.

Mukaiyama, Chem. Lett., 259 (1972).19. Oshima, et al., Bull. J., 48, 1567 (1975).20. Chem., 43,4915 (1978); M.

Matsuki, and S. Ito, Tetrahedron Lett.,1121 (1976); J. Biellmann and J. Ducep, ibid., 3707 (1969); E.

EVan Tamelen, et al., J. Soc, 94, 8228 (1972).21. Biellmann and D. Schirlin, Syn.

Coram., 8, 409 (1978).22. Noyori, Tetrahedron Lett., 311 (1970).23. Sotter and R. Soc, 95, 4444 (1973).24. Thiaclaisen, L. Brandsma, and H.

Verkraijsse, Rec Trav. Chim.Pays-Bas, 9^, 319 (1974); K. Yamamoto, and H.

Soc, 95, 4446 (1973). Evans, ibid.,100, 2242 (1978).25. GrSbel and D. Seebach, Synthesis, 357 (1977) and referencescited in section 5.1.26. Cookson and P. Commun., 990(1976) and 821,822 (1978).27.

Everhardus, H. Eeuwhorst, and L. Commun., 801 (1977); R. Grafing and L. Brandsma, Synthesis,578 (1978); R. Everhardus, R. Grafing and L.

Brandsma, Rec Trav.Chim. Pays-Bas, 97, 69 (1978).28.

Muthukrishman and M. Schlosser, Helv. Acta, 59, 13 (1976);J.

Chem., 44, 303 (1979).29. Rev., 78, 275 (1978) and referencescited in section IV.30. Sakurai, and T. Lett., 1483 (1977);T. Mimura, and A. Ari-Izumi, Tetrahedron Lett., 2425 (1977)and references cited therein.31.

Becker, unpublished results.-3-THE DESIGN, SYNTHESIS, AND BIOLOGY OF DNA INTERCALATING AGENTSReported by David W. RobertsonSeptember 27, 1979Intercalation is the noncovalent insertion of planar aromatic mole-cules between two successive base pairs of double-helical DNA.

SinceLerman's classic delineation of intercalation 1 over two decades ago, manyantitumor agents, mutagens, carcinogens, and teratogens have been found toexert their effects through intercalative binding to DNA. Because of thebiological and clinical importance of intercalation, molecular biologists,oncologists, and chemists have intensively investigated the nature of thisphenomenon. In this paper the evidence adduced for intercalation will besurveyed, and the design, synthesis, and biological applications of DNAintercalating agents will be examined.Structural Requirements for Intercalation. Ethidium bromide (1), aphenanthridinium trypanocide, and proflavin (2), a powerful frameshift mutagen,are archetypical intercalators (Figure 1). Both inhibit DNA and RNA synthesis 2and are two of the more widely studied intercalators. As these two examplesindicate, molecules which intercalate are planar aromatic molecules; largedeviations from molecular planarity in the form of bulky substituents such asin 2,7-di-t-butylproflavin 3 prevent intercalation. In addition to the endo-cyclic nitrogens which most high-affinity intercalators possess, many inter-calators also contain exocyclic amine groups.

These, if positioned properly,result in enhanced binding affinity. ^Figure 19 10 12H 2 N3 'NH 2proflavin (2)ethidium bromide (1)Methods by Which Intercalation and the Resultant DNA Deformations areStudied. In the normal DNA duplex, the adjacent parallel base pairs are invan der Waals contact with one another. A planar molecule is accommodated inthe helix by a local unwinding of the deoxyribose backbone; this separatesthe base pairs sufficiently to allow the insertion of the intercalator whilestill maintaining the integrity of the interbase Watson-Crick hydrogenbonding.

The DNA-intercalator complex is stabilized by many physicalprocesses; hydrophobic interactions, electronic interactions between the -rr-clouds of the intercalator and DNA bases, and hydrogen bonding have all beenshown to contribute to the stabilization of the complex. Because intercala-tive interactions perturb the physical and chemical characteristics of boththe DNA and the intercalator, a number of physicochemical probes can be usedto examine the interaction of an intercalator with DNA.Fluorescence and Visible Spectroscopy. Upon intercalation of ethidiumbromide into DNA, hypochromic and bathochromic shifts are produced in thevisible spectrum of ethidium. 5 When the intercalator is treated with-4-increasing concentrations of DNA, the absorbance spectrum of the drug shiftsprogressively towards a limit which represents the spectrum of the drug whenfully intercalated (Figure 2).

The curves pass through a well-definedisosbestic point, indicating that two forms of the drug, free and bound, arecontributing to the absorbance.Figure 2^V 1 1freefully complexed400 450 500 550 600Wavelength (nm)From a combination of the visible spectrum and a Scatchard plot, theassociation constant and number of binding sites in the DNA can be estimated.For ethidium bromide the approximate association constant is 5 x 10 M, withup to one ethidium per two base pairs being bound. The nonlinearity of theScatchard plots 5 and many other lines of evidence indicate that two types ofbinding are possible. After the high-affinity intercalative sites areexhausted, more positively charged ethidium molecules can interact with thenegatively charged phosphates of the DNA. At a ratio of one drug per nucleo-tide residue, an electrostatically neutral complex precipitates. 5When ethidium is complexed with DNA there is a dramatic increase in thefluorescence of the intercalator 6 (Figure 3). The most plausible explanationfor the fluorescence enhancement is the immersion of the ethidium into ahydrophobic region of the nucleic acid upon intercalation.

This reduces therate of excited state-solvent proton transfer, and increases the fluorescencelifetime by a factor of 12. 7Figure 31000Fluorescenceintensity 500300 400 500 600A (nm)NMR Spectroscopy. Numerous X H- and 31 P-NMR experiments have been con-ducted on mixtures of complementary oligonucleotides and intercalators. 8 10When 9-aminoacridine in D 2 is titrated with increasing concentrations ofdGpC, the nonexchangeable protons experience a linear upfield shift untila 1:2 acridine-dinucleotide stoichiometry is reached 11 (Figure A).

Thissuggests the formation of a minihelix with the acridine sandwiched betwef n-5-Figure 459i ri i— r—— r—60si-2^6.1.o'I'a-. 0.5 ppm (H-l, H-10) relative to the corresponding protons in uncomplexedethidium. 12 Calculated values for the upfield shifts based upon the atomicdiamagnetic anisotropy and ring current contributions compare favorably withthe experimentally determined values.Circular Dichroism and X-Ray Studies. When ethidium is mixed with7—9double-helical DNA, circular dichroism is induced in the nonchiral ethidium. RVarious dichroism studies have indicated that the plane of the inter calator isapproximately parallel to the planes of the adjacent base pairs.Complexes of intercalators and complementary oligonucleotides can some-times be crystallized, allowing the direct visualization of inter calativebinding in a miniature double helix. 13 All the X-ray studies confirm thepostulates which were based on spectroscopic data.Hydrodynamics.

Intercalation, because of the necessary local unwindingof the helix, results in a lengthening and stiffening of the DNA molecule.This causes the intercalated DNA to become more rod-like than its pristinecounterpart; as a consequence the intrinsic viscosity of DNA solutions isincreased. 1 Because the additional length due to an intercalator is approxi-mately the same as that of an additional base pair and most intercalatorsare of less molecular weight than a base pair, the average molecular weightper unit length of the DNA decreases; this results in a decrease of thesedimentation coefficient. 1A unique method of studying intercalation is the interaction of theintercalating agent with covalently closed, supercoiled DNA. These DNAsdisplay large changes in their supercoiling as a result of local intercalativehelix unwinding. ' 5 As increasing concentrations of intercalator are added,the right-handed supercoiling decreases until open circles are obtained.Additional intercalating agent results in more unwinding until torsionalstrains produce left-handed supercoils (Figure 5). The progress of the titra-Figure 5-^right-handedleft-handed-6-tion is most conveniently monitored by changes in the sedimentation coeffi-cient of the DNA (Figure 6).

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All known intercalating agents remove andreverse the supercoils of closed circular duplex DNA.Figure 6right-handedsupercoilsleft-handedsupercoilsopen circles0.02 0.06 0.1drug molecules bound per nucleotideIntercalative Photoaf f inity Labelling Reagents. Intercalators such asethidium bromide have been widely used to probe numerous biological structuressuch as tRNA, 5S-RNA, and chromatin; they have also been of great utility instudies of biological processes such as DNA replication and transcription,and the mechanism of frameshift mutagenesis. 16 One of the major disadvantagesof using noncovalently attached intercalators in the study of biologicalstructures and processes is that during the time of a biological or physicalassay the intercalators can move from site to site. 17 In in vivo studies,cell fractionation techniques can rearrange concentration gradients and drugdistributions among subcellular compartments. 18 This problem can be circum-vented by the use of intercalating agents which can be covalently attachedto the DNA or juxtaposed proteins. Photoaf f inity labelling is a techniquewhich permits this covalent attachment.

At least two different types ofintercalative photoaf f inity labels have been developed: the furocoumarins(Figure 7) and azide analogs of ethidium and acridine.Figure 7psoralin (3)angelicin (A)The furocoumarins are a group of naturally occurring and syntheticcompounds which manifest interesting photobiological effects such as skinThey have been used therapeutically since antiquity; thesensitization,19fruit and seed extracts used by the ancient Egyptians to treat vitiligocontained furocoumarins. 20 A more recent medicinal application is thephotochemo therapy of psoriasis and other skin diseases19The mechanism by which furocoumarins exert their photobiological effectsis photoreaction with DNA; a linear relationship normally exists between the-7-biological effects and the extent of photoreaction.

2 1 In the absence ofelectromagnetic excitation there is no disruption of cellular processes.Furocoumarins intercalate into DNA and form cyclobutane adducts with thepyrimidine bases in DNA when the complex is irradiated with 365 nm light.^The linear furocoumarins, the psoralens (Figure 7), are capable of formingeither monofunctional or difunctional adducts with DNA. The difunctionaladducts are due to the reaction of both the 3,4 and 4', 5. double bonds withpyrimidine bases in each strand of duplex DNA. This crosslinks the DNAstrands and prevents them from becoming separated even under conditionswhich normally denature DNA. The crosslinking has been demonstrated bydenaturation-renaturation kinetics 22 and by electron microscope studies. 23Cole has shown that the inhibition of certain bacterial functions by psoralinis approximately equal to the rate of formation of a single psoralen cross-link per DNA molecule. 24Numerous derivatives of psoralen have been prepared in order to optimizetheir DNA interaction characteristics.

Hearst and Rapoport reported 2 - 5 that4'-aminomethyl-4,5 l,8-trimethylpsoralen is the best derivative for photo-reaction with DNA. It can bind to DNA to the extent of one drug moleculeper five base pairs with a 65% photoattachment efficiency.The angular furocoumarins, the angelicins (Figure 7), form only mono-functional adducts and have a low ability to produce photosensitized effects.^The angelicins, however, may be the furocoumarins of choice if inhibition ofDNA or RNA synthesis is the only desired biological effect. Crosslinking isa very severe type of damage to a cell's genome and often leads to undesirableresults.9-Azidoacridine, another type of intercalative photoaffinity label, wasprepared to help elucidate the mechanism of 9-aminoacridine ' s frameshiftmutagenicity. 26 Surprisingly, 9-azidoacridine is not a frameshift mutagen;it is a base pair substitution mutagen with or without photolytic activa-tion. Placing the azide moiety at other positions on 9-aminoacridine wouldperhaps yield a photoaffinity label which still maintains the frameshiftmutagenicity of the parent compound.A more suitable photoaffinity label for the frameshift mutagen studiesis the fluorescent intercalator 8-azidoethidium bromide. 7 18 27 Structure-activity relationships of various phenanthridinium analogs of ethidiumbromide indicated that the 8-amino group could be modified with littlechange in its interaction with DNA.

4 This was found to be true with 8-azidoethidium bromide. In the dark, 8-azidoethidium bromide and ethidium bromideare competitive inhibitors in DNA binding studies and cause similar pertur-bations in the hydrodynamic properties of native DNA. The azide analogbinds strongly to DNA (K a =2-3xl0 5 M 1 ), and can be photoattached to DNAwith efficiencies approaching 75%. 27 Unlike 9-azidoacridine, 8-azidoethidiumbromide behaves as a frameshift mutagen both before and after covalentattachment to DNA.Antibiotic Intercalators. Many naturally occurring antibiotics havebeen shown to exert their effects through intercalative binding to DNA.The actinomycins, 28 ' 29 quinomycins, 30 and triostlns 31 all intercalate intoDNA with very high affinity. The two most heavily studied intercalatorsare actinomycin D (5, Figure 8) and echinomycin (60, a member of thequinomycin antibiotic family.

Both of these compounds differ from pre-viously mentioned intercalators in that they have peptide moieties, and-8-after incercalation of the chromophore, these peptides lie in the minorgroove of the DNA.