Daniel P. Zaleski, Susanna L. Stephens, Nick R. Walker

School of Chemistry, Bedson Building, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.

Evidence from Broadband Rotational Spectroscopy for a Complex Between AgCCH and C6H6

Anthony C. Legon

School of Chemistry, University of Bristol, Bristol BS8 1TS, UK.

The Ohio State 69th International Symposium on Molecular Spectroscopy, June 20th, 2014.

Metal Antitumor Agents

In principle, three different groups of metal-containing antitumor agents can be distinguished:

inorganic complexes composed of a central metal atom surrounded inorganic ligands

- been much clinical success against carcinomas of the head and neck

organometallic complexes containing one or more metal atoms as well as organic ligands, the ligands being linked to the metals by direct carbon-metal bonds

complexes also including metal atoms and organic ligands but lacking carbon-metal bonds

- Antiproliferative activity against e.g. Ehrlich ascites tumor, sarcoma 180, B16 melanoma, colon 38 carcinoma, and Lewis lung carcinoma

cisplatin

Chem. Rev. 1987, 87, 1137-1152.

Metallocene,M = Transition Metal

Benzene-AgX Complexes

Early-transition-metal compounds have shown tumor-inhibiting efficacy.

Mainly represented by metallocene complexes where M = Ti, V, Nb, Mo, Cu; and e.g., X = Cl

Focus on silver containing species:- Same column as Cu: similar electronic properties- Two isotopes ~50% abundance (important for structure determination)- Lacks quadrupolar nucleus- Experimentally easier to work with compared to other TM’s

Benzene is the classic biological analog.

Angew. Chem., 1979, 91, 509.Angew. Chem., Znt. Ed. Engl., 1979, 18, 477.Z. Naturforsch. B: Anorg. Chem., Oig. Chem., 1979, 34B, 805.Z. Naturforsch. C Biosci., 1979, 34C, 1174.J. Znorg. Nucl. Chem., 1980, 42, 1789.ACS Symp. Ser., 1983, No. 209, 315.

Spectroscopy of Metal-Ringed Species

JACS, 2004, 126,10981-10991.

Vibrational/DFT study of Be-M+

Organometallics, 1999, 18,1430-1438.

Mass Spec study of Be-M

TB01: Cp-ReCH3(CO)(NO)

Chirped Pulse FTMW Spectroscopy

Broadband spectrometers with instantaneous frequency coverage from 2-8 GHz, 6.5-18.5 GHz, 18.5-26 GHz, and 25 – 40 GHz have been constructed.

Current Technology:AWG 24 Gs/s (12 GHz)Digital Oscilloscope 100 Gs/s (33 GHz)

~60x

~3M FID’s~100 hr

C6H6-AgCl

Parameter Experiment*M062X

aug-cc-pVTZ†

B (MHz) 867.5635(12) 670.6502

DJ (kHz) 0.03954(822) 0.222

DJK (kHz) - -0.198

χaa (MHz) -24.2(14) -23.5

Nlines 9 -

RMS (kHz) 6.14 -

* C6H6-107Ag35Cl† Ag: aug-cc-pVTZ-PP

Chem. Phys. Lett., 1997, 272, 61-68.

20 cm-1

Assigned Species

C6H6-107Ag35ClC6H6-109Ag35ClC6H6-107Ag37ClC6H6-109Ag37Cl

C6H5D-107Ag35ClC6H5D-109Ag35Cl

Structure A (MHz) B (MHz) C (MHz) B (MHz) DJ (kHz)Sym Top - - - 867.5635 0.0350Asym Top 2642.9990 868.6841 866.4636 867.5740 0.0868

C6V 2805.2121 791.8712 791.8712 791.8712 2*10^-9Minimum 2842.9929 720.9477 717.8263 719.3872 0.1433

1 2589.3667 759.6317 739.6489 749.6441 6.64012 2658.9544 847.0038 823.9803 835.4927 8.82843 2875.3505 933.7453 905.1196 919.4252 12.60194 3280.0492 1028.8637 965.4478 996.8203 48.38685 2648.1059 728.7234 710.4239 719.5785 5.33866 2746.2920 790.3695 755.7916 773.0506 17.93817 2948.2350 852.9360 792.6311 822.4423 46.75798 3250.8617 912.5184 818.5120 864.1349 91.05089 1733.2704 1003.2471 815.4387 867.1255 168.0033

C2V 5663.4018 312.9461 296.5590 304.7555 1.5634min-5A 2756.622 287.6286 286.7459 287.1873 0.0099

min-4.5A 2743.323 336.5123 335.1410 335.8267 0.0244min-4A 2726.3418 397.4721 395.2479 396.3601 0.0663

C6V-2.0A 2830.6040 856.7624 856.7624 856.7624 2*10^-9tilted-2.0A 2653.2633 900.7231 872.9112 886.8044 13.0950tilted-3.0A 2424.3407 603.6883 580.6290 592.1594 8.8153tilted-4.0A 2333.6614 418.6347 404.7867 411.7149 3.0888tilted-5.0A 2235.4943 296.8520 288.1923 292.5242 1.2018

Asymmetric Possibilities

M062X/SDD

Structure Determination

(A,B,C) = (IA,IB,IC)

I = Σ mi∙ri2

(Aˊ,Bˊ,Cˊ) = (IAˊ,IBˊ,ICˊ)

|ra|,|rb|,|rc|

Isotopic substitution produces small (and predictable) shifts in the rotational constants

that are site-specific.

Free from other assumptions about the molecular structure

Am. J. Phys. 1953, 21, 17.

r(Be-Ag) = 2.043(9) Å

r(Ag-Cl) = 2.240(7) Å

MP2/aug-cc-pVTZ-PP

X-AgCl Trends

J. Chem. Phys., 2011, 135, 024315.

Species χaa (MHz) r(Ag-Cl) (Å)

AgCl -36.4 2.281

-Ar -34.5 2.285

-Kr -33.8 2.277

-Xe -32.2 2.271

-H2O -32.3 2.272

-NH3 -29.8 2.263

-H2S -29.4 2.255

-C2H2 -28.9 2.266

-OC -28.2 2.255

-C2H4 -27.9 2.272

-C6H6 -24.1 2.240

2.8 Å

radiusVDW(Ag) ~ 2.1 Å

New J. Chem., 2007, 31, 832-834.

r(Be-Ag) = 2.043(9) Å

r(Ac-Ag) = 2.184(8) Å

0.254

-0.731

-0.432

0.432

MP2/aug-cc-pVTZ-PP

Recap

Experiment r(Be-Ag) = 2.043(9) Å

Theory calculates r(Be-Ag) = 2.195 Å

Exp TheoryAsym*

TheorySym*

B (MHz) 867.5635(12) 756.8813 833.1309

DJ (kHz) 0.03954(822) - -

DJK (kHz) - - -

χaa (MHz) -24.2(14) -22.7 -31.3

r(Ag-Cl) (Å) 2.240(7) 2.245 2.266

* MP2/aug-cc-pVTZ Ag: aug-cc-pVTZ-PP

C6H6-AgCCH

~20x

~3M FID’s~100 hr

C6H6-AgCCH

21 cm-1

Parameter Experiment*MP2

6-311++G(d,p) †

B (MHz) 791.03578(20) 739.32668

DJ (kHz) 0.0230(12) 0.205

Nlines 7 -

RMS (kHz) 2.13 -

* C6H6-107AgCCH† Ag: cc-pVDZ-PP

Assigned Species

C6H6-107AgCCHC6H6-109AgCCHC6H6-107AgCCDC6H6-109AgCCD

Structure Determination (?)

r(Ac-Ag) = 2.210(1) Å

r(Ag-H) = 4.284(1) Å

r(Be-Ag) ~ 3.0 Å

r(Ag-H) = 4.367(2) Å

J. Chem. Phys., 2014, 140, 124310.

Recap

Experiment suggests r(Be-Ag) ~ 3.0 Å

Theory calculates r(Be-Ag) = 2.194 Å

Exp TheoryAsym*

TheorySym†

B (MHz)791.03578(20

)739.32668 843.4128

DJ (kHz) 0.0230(12) 0.205 -

DJK (kHz) - 1.222 -

r(Ag-H) (Å) 4.367(2) 4.270 4.256

* MP2/6-311++G(d,p) Ag: cc-pVDZ-PP

† MP2/6-311++G(3df,3dp) Ag: aug-cc-pVTZ-PP

Conclusions

Be-AgX (X = Cl, CCH) likely has C6v symmetry- Although Be-AgCCH remains uncertain

Strong overlap between the π-density and the Ag atom- Likely due to Ag atom size- Shorter Be-Ag distance than Ac-Ag (at least for AgCl)- Is there a system small enough to favor the ring edge?

Proper modeling left to do- Need frequency calculations- Ab initio seems to be underestimating the interaction

Acknowledgments

Engineering and Physical Sciences Research Council

AWE (Aldermaston)

University of Bristol David Tew Wataru Mizukami